#Gene editing for sperm count

[yellowivfgurgaon]

Latest Treatments for Low Sperm Count in 2025: Effective Solutions for Male Infertility

In 2025, low sperm count remains one of the leading causes of male infertility, but thanks to remarkable advancements in fertility treatments, men struggling with this condition now have more hope than ever before. Low sperm count, or oligospermia, can be a frustrating and emotional barrier to starting a family, but new innovations in medical technology and personalized treatment approaches have made a significant impact in overcoming this issue.

Whether you���re just starting your fertility journey or have tried other options without success, understanding the latest treatments for low sperm count in 2025 can help you make informed decisions. This article highlights cutting-edge therapies, lifestyle interventions, and advanced medical solutions that can significantly improve sperm quality and quantity, providing better outcomes for couples seeking to conceive.

What is Low Sperm Count?

Low sperm count (oligospermia) refers to a condition where a man has fewer sperm in his ejaculate than the average count necessary for conception. The World Health Organization (WHO) defines normal sperm count as 15 million sperm per milliliter of semen. Anything below this threshold is considered low, which can lead to difficulties in fertilizing an egg naturally.

Causes of low sperm count can vary, ranging from lifestyle factors such as smoking, excessive alcohol consumption, and obesity, to medical conditions like varicoceles (enlarged veins in the testicles), hormonal imbalances, or genetic conditions. However, new and innovative treatments in 2025 offer promising results for men with oligospermia.

Latest Treatments for Low Sperm Count in 2025

1. Microfluidic Sperm Sorting (MSS)

Microfluidic sperm sorting is one of the most significant advancements in male fertility treatment in recent years. This non-invasive technology utilizes a microchip-based device to sort sperm cells based on their size, motility, and quality. The result is a selection of the healthiest and most viable sperm for use in fertility treatments such as intrauterine insemination (IUI) or in vitro fertilization (IVF).

Unlike traditional sperm washing techniques, which can result in sperm damage, microfluidic sperm sorting ensures higher-quality sperm are selected, improving the chances of successful fertilization and reducing the risk of genetic abnormalities.

2. Hormonal Therapy Tailored for Male Infertility

In 2025, personalized hormonal therapy has become a go-to solution for men with hormonal imbalances affecting sperm production. Hormonal treatments, including human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH), are designed to boost testosterone levels and improve sperm production.

By customizing hormone therapy based on each individual’s specific needs and hormone levels, doctors can create a more effective treatment plan, leading to significant improvements in sperm count and quality.

3. Gene Editing and CRISPR Technology

Gene editing technologies like CRISPR are now being explored as potential treatments for male infertility caused by genetic mutations. In cases where low sperm count is linked to specific genetic abnormalities, CRISPR may one day offer a solution by correcting these mutations at the DNA level.

Although this treatment is still in the experimental phase, research in 2025 has made significant strides, showing promise for the future of male infertility treatments.

4. Varicocele Embolization and Surgery

Varicocele, a condition in which veins within the scrotum become enlarged, is a leading cause of low sperm count. In 2025, varicocele embolization and microsurgery have become increasingly effective and minimally invasive options for treating this condition. These procedures improve blood flow and reduce heat around the testicles, which can help restore sperm production and improve sperm quality.

Varicocele embolization, in particular, is a non-surgical procedure in which a catheter is used to block off the enlarged veins, allowing for quicker recovery and fewer complications compared to traditional surgery.

5. Stem Cell Therapy for Sperm Regeneration

Stem cell therapy is a groundbreaking treatment that holds immense potential for treating male infertility. In 2025, researchers have made significant advances in using stem cells to regenerate damaged or underdeveloped testicular tissue responsible for sperm production. This regenerative approach could restore normal sperm production in men who have suffered from testicular injuries or illnesses that result in low sperm count.

Stem cell therapy is still in the early stages of development, but it is a promising area of research that may soon become a standard treatment for male infertility.

6. Lifestyle Changes and Nutritional Supplements

While advanced medical treatments are crucial, lifestyle changes and nutritional supplements continue to play a vital role in improving sperm count. In 2025, fertility specialists emphasize a holistic approach to male fertility, which includes:

Maintaining a healthy weight: Obesity is strongly linked to reduced sperm quality, and weight loss can lead to improved sperm count.

Quitting smoking and limiting alcohol: Both habits have been shown to negatively impact sperm production and motility.

Supplements: Antioxidant-rich supplements such as coenzyme Q10, zinc, and vitamin E have been proven to improve sperm quality. In 2025, new fertility supplements formulated with optimal doses of these antioxidants are readily available and more effective than ever.

7. Testicular Sperm Extraction (TESE)

For men with extremely low sperm counts or azoospermia (no sperm in the ejaculate), testicular sperm extraction (TESE) is an effective treatment option. TESE involves surgically retrieving sperm directly from the testicles, which can then be used for IVF or ICSI (intracytoplasmic sperm injection).

In 2025, advances in microsurgical techniques have made TESE less invasive and more successful, offering hope to men who previously had limited options for fertility treatment.

How to Improve Your Chances of Success with Low Sperm Count

In addition to seeking medical treatment, there are steps you can take to improve your chances of conception when dealing with low sperm count:

Timing Intercourse: Understanding your partner’s ovulation cycle and timing intercourse accordingly can increase the likelihood of conception.

Reduce stress: Chronic stress can affect hormone levels, which in turn can impact sperm production.

Avoid exposure to toxins: Limiting exposure to environmental toxins, such as pesticides, heavy metals, and chemicals found in plastics, can help protect sperm health.

Final Thoughts

The treatments for low sperm count in 2025 have advanced significantly, offering more hope and effective solutions for men struggling with infertility. Whether you opt for innovative medical interventions like microfluidic sperm sorting or take a holistic approach by improving your lifestyle, the key is to stay informed and proactive in your fertility journey. With the latest advancements, the path to parenthood is more achievable than ever before.

[timeisacephalopod]

Have a TonyRhodey AU in which Tony is complaining about his children to Rhodey, who is not at all lost on the fact that Tony’s kids act like him so its kind of funny that he’s mad about it.

*

Rhodey laughs, hand covering his mouth and Tony lets out a noise of frustration. “Stop that! You don’t get it, Peter was being deliberately stupid. Like who decides to walk up to the cops with information on the asston of property damage and say ‘do you want the tea?’ instead of just telling them what happened?”

He doesn’t say anything about that time he and Tony got into a nasty car wreak that neither of them should have survived let alone come out untouched only to tell the cop that he’d rather be eating a burger than talk to them. And he did this for an hour until he got the damn food, then he continued to purposefully badger the cop because he thought it was funny. So its really not shocking that Peter thinks irritating the cops is funny too, he comes by it honestly. “That’s pretty funny,” he says and Tony’s eyes bug out of his head.

“No! Give him those ‘respect cops’ talks you always gave me, shithead!”

Rhodey squints, “I gave you ‘don’t torment cops with your black friend in shooting range’ lessons, lets not twist things. And no, parent your damn self you were the one that adopted like fifty kids.”

“Excuse you we have three and one is part time Pepper’s so she barely even counts so really we have two kids and a pest,” Tony says. “Fifty kids my ass. And you’re his parent to, do parent things,” he says, poking Rhodey in the side.

He smacks Tony’s hand away, “stop that. And Morgan is your actual child, how’s she count less?”

“Because Pepper has her equal time, Rhodey. And they’re all my actual kids, just because one was once a sperm that was-”

“Okay, you don’t need to finish that sentence. Peter sassing the cops is so not the worst thing he could be doing. Remember that ridiculous Jake Gyllenhaal looking bastard with the fish bowl head? Absolutely worse shenanigans than asking the cop if he wants the tea. Just saying.” And Peter is a good kid too, the least troublesome one they have and the little bastard got bit by a radioactive spider and became a superhero. But he’s the least troublesome kid they have. Sometimes Rhodey wonders if Tony is secretly Harley’s actual father because they share way too much in common and how come none of the kids are like him? Rude.

“Fine, Peter being a dick to cops is fine. Harley nearly died twice because, and this is a quote, ‘I wanted to make a cool Tik Tok.’ I had to look up what the fuck that was,” Tony says, exasperated.

Yeah, Harley is a certified Dumb Bitch but if Tik Tok and superheroes had been around in their youth he knows he’d have to find a way to save Tony’s dumb ass as he made videos in the middle of superhero battlefields. Shit, if that was the case in their youth deciding to make cool videos would have been Iron Man’s origin story instead of the terrorist thing.

“Tones you know you’d do the same thing, you can’t really judge the kid,” he says reasonably.

If it were possible for steam to blow out of Tony’s ears it would have. “He almost died twice under crumbling buildings for a twelve second video with Mii music in the background captioned ‘my last brain cell trying to avoid death while I ruin my life.’ He almost died twice for that,” Tony says like he didn’t once give out his personal address to terrorists only to be surprised when they blew up his house. And that’s one of the less dumb things Tony has done that’s nearly resulted in his death.

“Uh huh. Baby I hate to tell you this, but he’s just acting like you,” he says, wincing a little as he says it.

Tony reacts exactly how he thinks he would, mostly offended about it. “Rhodey, that is the problem. I’m an idiot, I like to think I have raised my kids to not be idiots.”

“Eh,” Rhodey says, waving hand. Tony smacks him playfully.

“Don’t be rude and talk to the kid, he listens to you,” he says like Harley doesn’t listen to him too.

“Its a phase, he’ll get through it,” Rhodey says.

“He almost died for a twelve second video that is an insane phase! Why are you not worried about his safety?” he asks, confused.

“I’m assuming this was the same event where Peter asked the cops if they wanted the tea, yeah?” he asks.

Tony huffs, “that’s not the point.”

“Is so. I know you wouldn’t let anything bad happen to him and neither would Peter, he was fine. Stupid, but fine. Besides, I can’t talk braincells into the kid,” he points out. “Didn’t work on you anyway.”

“Well... can you just talk to him?” Tony asks, shoulders slumped.

Rhodey shrugs, “yeah, alright. I doubt I’ll do more than you did but I can talk to the kid.” Tony nods, visibly relieved and Rhodey waits for him to go on but he doesn’t. “And Morgan?” he asks, figuring she’s gotten into some kind of something this week. Last time he got an update she tried to bleach her hair so she could dye it pink except she’s five so that didn’t go well and Tony spent a lot of time yelling about potentially going blind while Morgan watched on. Her only defense was that she’s not dumb, she knows not to bleach her eyes.

He’d had to leave that alone too and he and Pepper had a quiet moment about how Tony one hundred percent would have done the same thing. Kind of did in college when he decided to go blond and he looked awful. Then he decided the solution was shaving his hair short, which mostly made him look like a skin head so Rhodey told him to dye his hair back but Tony’s dramatic ass hid under the bed for a month until it grew out enough to leave for more than a few hours at night to eat, shit, and shower. So really, Morgan was just reaching out to some Stark genes there and she was fine, if sporting some awful hair, so he and Pepper got a good laugh out of Tony’s reaction.

“Oh she’s fine, turns out she’s a music prodigy so there's that. But I’m sure she’ll do some stupid thing soon. In the meantime though she’s not doing anything particularly stupid so that’s nice, I’ve got my hands full with Harley and Peter anyway.”

That doesn’t surprise Rhodey much, she insults Tony’s music taste too much to not know things about it. “Guess she had some insight when she told you Alice Cooper was worse than Barney,” he says and Tony makes an offended noise.

“She did not!”

*

Rhodey looks over the kids sternly until Morgan raises her hand. “I didn’t even do anything so can I leave?” she asks. He nods and she grins, taking off presumably to go harass Tony about his music that she’s deemed awful. Tony has threatened to disown her four times today alone.

Harley and Peter wilt a little and Rhodey sighs. “Harley, nearly dying for a Tik Tok is not nearly a cool enough death to risk it. Peter, that’s hilarious. Keep pissing off New York’s finest, you’re bullet proof anyway. Stop doing it in front of your father though, I’m tired of Tony losing his ass about it.”

Peter frowns, “I’m not bullet proof.”

“I rescind that, stop pissing off New York’s finest, I don’t put it above at least one of them to shoot Spiderman. Harley, learn how to edit, man. What the hell are you doing running around in superhero battles for? Go ask Ned if you need help with it, you know Ned is good at editing and he’s a good boy, I’m sure he’d help you.” Helped Peter hack into his suit and they both thought Tony didn’t know right away like he didn’t plan for the possibility that someone would tamper with the suit Peter or otherwise. Ned got himself a job out of it and Peter got grounded, which meant no Spiderman.

“Please don’t call Ned a good boy,” Peter says, wrinkling his nose.

“Hey, I found another Spiderman and his suit is way cooler than Peter’s!” Morgan says from behind them. Rhodey turns to find a kid standing there in an admittedly very cool design but its clearly painted over one of Peter’s suits. He’d recognize one of those suits anywhere the design is so unique. He turns to Peter, who smacks Harley.

“You said he was well hidden!” he hisses.

“Morgan’s a busybody, you know that!”

“He was in your closet, that’s not well hidden. You should have hid him under the sink,” Morgan tells them, hands on her hips.

Rhodey lets out a long suffering sigh. “Alright kid, who are you?”

“I’m not Miles Morales. I’m some other guy,” he says, looking away and Rhodey hopes this kid has loving parents because he’s absolutely dumb enough for Tony to adopt.

“Yeah alright, lets get you to the lab so you can get your own suit. Peter, you can explain yourself to your father and Harley, you too. Morgan... good work,” he says awkwardly but Morgan looks proud of herself so at least there’s that. Miles looks upset that he’s outted himself but it does seem like Peter is incapable of finding friends who are good liars. Better for him and Tony though so he’ll take it.

[hellyes-tommccamus]

Trinity (2003) [film]

Sci-fi/drama

Tom McCamus plays a main role

I was so excited to finally see this movie. A weird, low budget indie British movie? Yes please.

Tom McCamus plays Dr Clerval, a scientist working at a remote research station. He is taken prisoner by investigators Shiller (Lucy Akhurst) and Brach (Stephen Moyer). At least Shiller believes it is him, he claims to be a clone of the doctor. It’s an intense, unsettling film.

The stylistic choice to use mostly harshly lit closeup shots works for this film, and showcases Tom’s skill at conveying nuances of meaning and emotion with the smallest of movements.

I could listen to Tom talking about genetics all day long, but being both a scientist and a pedant I have to point out that DNA does not contain proteins (okay fine, histones, but those are for structural and control purposes and don’t contain genes). Transcription and translation have to happen before you get to proteins.

Also he talks about fertilisation of clones made by somatic nuclear transfer. That’s actually not necessary, as somatic cells contain all the genetic material needed to make an individual. An ordinary egg needs to be fertilised as it contains only half of the genetic material, and the sperm brings along the other half.

Thirdly, a “clone” which has been screened for undesirable traits isn’t an exact copy of its original. And screening isn’t exactly the right word; from the context, CRISPR gene editing (which didn’t exist at the time) would be more accurate. Screening is more like checking for genes linked to diseases or undesirable traits. In general what he talks about is real science. It’s how Dolly the sheep was made. And genes for personality might sound fake, but I have read papers which prove there is truth in that.

However, his statement about eugenics is complete balderdash. It was and is not effective. Because we have two sets of alleles which control each trait (this is a simplification), dominant genes mask the appearance of recessive genes, so heterozygous individuals (with one “strong righteous” gene and which hides its partner the “undesirable proletarian” gene) will escape any eugenics program and those terrible undesirable proletarian traits will arise again when two heterozygous individuals have children.

Poverty, disease and disability are not entirely caused by heritable genetic traits (poverty is not at all, in fact).

Dr Clerval’s program involves screening individuals to find the best example of every gene in order to produce the best human. He admits that this is down to his opinion.

I’m sure everyone will agree that is not a good idea. But I can tell you that it is also scientifically flawed. A genetically identical population is a vulnerable population, which can be wiped out by a single disease. It is also unable to adapt to change. You might create the perfect human for a particular ecological niche in the current time, but as the environment changes, this population of clones would all become unfit to survive.

There are certainly copies of genes that do not work correctly and are deadly if you inherit them, but there is not a single “best” gene. Otherwise evolution would weed out the unfit genes naturally. Evolution is more accurately described as “survival of the fit enough” not “survival of the fittest”. I’m not the fittest human by any stretch of the imagination, and I’m sure that neither are you. But we are fit enough to survive and that’s all that counts.

I appreciated the fact that “clone” Clerval has grey hair, as this hints at the ageing problem that often plagues clones. As we age, our cells must divide to produce new ones, and the ends of chromosomes (the telomeres) shorten. Many animal studies have shown clones to have shortened telomeres when they are created/born and suffer from the effects of ageing sooner.

The genetics aspect of the film is left a mystery, or forgotten about in favour of weird mind games, which was a little disappointing. I would have liked to know more about Dr Clerval’s experiments and the other clones.

[heliosphoenix]

2017 in review!

That’s right folks, as we count down the hours left until the new year, it’s time once again for Helios’ fucking awesome review of the year we just had.

I think it’s safe to say that 2017 was a very...weird year. That’s probably the best was I can describe it. And I’m not just saying that because somehow a reality TV star became the (supposed) leader of the free world, it just seemed like there were a lot of things that happened this year that just made us wonder, as a species, “Just what the heck are we doing?!”

But, like Taylor Swift, I’m not going to act like the year was all gloom and doom (and fuck you Buzzfeed for trying to pretend that’s all it was). Cause even though 2017 was full of things that seemed bad, or even just weird, there were still a lot of good things that happened as well, and we need to remember them. Because I’ll be damned if I’m going to let clickbait distract us from the fact that there were moments where we lit up the darkness.

Here’s some of them:

The Women’s March on January 21st was one of the largest protests ever with 2 million people taking part.

Scientists in China discovered our oldest ancestor yet, a 540 million year old Saccorhytus

The New England Patriots won Super Bowl LI capped by an incredible comeback in the second half, Tom Brady wins his 5th ring and arguably cements his status as the greatest NFL QB of all time.

Adele won best song and best album at the Grammy’s.

A mostly underwater continent called Zealandia was discovered in the South Pacific.

7 planets roughly the size of Earth were discovered around the star Trappist-1, 3 of which could possibly support life.

“Moonlight” upset “La La Land” for Best Picture at the Oscars (literally at the last moment!)

The world’s oldest golf club in Scotland voted to admit women as members for the first time. 

Carrie Lam became the first woman to be elected chief executive of Hong Kong.

The largest Dinosaur footprint ever measured (at 1.7 meters) was found in Western Australia.

Bob Dylan won the Nobel Prize for Literature.

Edward Enninful became the first black man to become editor of Vogue.

France declared mandatory labeling of digitally modified photos of fashion models.

Emmanuel Macron defeated Marie Le Pen in France’s Presidential election.

MTV became the first major awards show to adopt gender-neutral categories.

Apple became the first company to be worth more than $800 billion.

Brazil declared the national emergency as a result of the Zika virus was over. Puerto Rico also declared its own Zika epidemic had ended.

A global ransomware attack was halted after a 22 year old UK blogger stumbled on the kill switch.

Japanese researches reported the birth of mice that were fertilized by freeze-dried sperm stored on the International Space Station.

The Golden State Warriors won the 2017 NBA championship after posting an unprecedented 16-1 record in the postseason.

Facebook reached 2 billion users.

Columbia rebel group FARC disbanded after 52 years.

France announced it will ban petrol and diesel powered cars by 2040. Great Britain soon announced a similar ban.

Tesla produced it’s first mass-market car, the Model 3. Elon Musk is of course the first owner.

Jodie Whittaker became the first female Doctor on Doctor Who.

Despacito became the most streamed song ever.

John McCain cast a decisive vote to strike down an attempted repeal of the Affordable Care Act.

Gene editing in human embryos to eliminate disease causing mutations was successful performed for the first time.

Scientists identified a deficiency in nicotinamide adenine dinucleotide (NAD) as being a major cause of birth defects and miscarriages.

A 100 year old fruitcake was discovered in Antarctica in a hut used by the expedition of Robert Falcon Scott, and it was almost edible! 

Paris and Los Angeles were announced as the hosts for the 2024 and 2028 Olympic Games.

The Cassiopeia Jellyfish was discovered to be the first brainless animal that can sleep.

The first woman graduated from the US Marine’s Infantry Officer Corps.

The first Ichthyosaur fossil was found in India.

The painting “Salvador Mundi” by Leonardo Da Vinci sold for $450.3 million.

A rainbow in Tapei was recorded lasting nearly 9 hours, the longest ever.

Gay marriage was legalized in Australia.

Doug Jones became the first Democratic Senator from Alabama in 25 years.

The Vatican rediscovered long lost painting by Raphael.

The Asteroid Oumuamua was discovered to be an interstellar object.

Two neutron stars collided and confirmed the existence of Gravity Waves.

SpaceX launched and recovered a reused Falcon 9 rocket for the first time.

How about the movies that came out this year? Spider Man, Guardians of the Galaxy 2, Wonder Woman, Thor: Ragnorok, Star Wars.

The Michigan Basketball Team won the Big Ten Tournament after surviving a plane crash.

THE GREAT AMERICAN ECLIPSE. How can anyone forget that day?

As you can see, there’s a lot that happened this year! A lot of stuff that ranged from interesting to amazing. And even though there people in this world that are still hell bent on convincing us that everything has gone to rack and ruin, we must never forget that there are still a lot of good things that happened this year, and will continue to happen in the year ahead.

Even so, there’s been a lot of talk this year about where we’re going as a culture, a society and a species. There’s people who feel, for a variety of reasons, that we’re heading on the path to destruction, or at the very least have strayed from the path we should be on. And everyone seems to have the same question; “How do we get back on the right track?”

Well, here’s a suggestion for creating the world you want to live in:

Try spending the next year doing the things you want to do and being the person you want to be.

You don’t need to post a hashtag or join a protest to make a difference. Donate to a charity or help a friend in need. Maybe offer to drive someone who’s not feeling well to the doctor, or go clean the yard of one of your elder neighbors. Or just do what you can to promote the values you believe in. Why wait for a day of action or some galvanizing event? You can do this stuff right now.

You don’t need an incendiary tweet to take action, just try to do the right thing every other day.

Instead of trying to focus on how you can get the entire world onto the right path, why not start with just yourself and your immediate friends and family. Become an inspiration for your fellow citizens, lead by example. 

And most of all, never forget to look for the light. It’s hard to light a candle, and much easier to curse the dark instead. But as President Kennedy once said, we do these things “Not because they are easy, but because they are hard.”

Now as always, there’s one more good thing that happened this year, and you are gonna tell me what it is. Because I guarantee you that even if you’ve just had the worst year ever, there was something good that happened. Maybe someone got you a gift you really wanted, or you reconnected with a friend you didn’t even know you were missing, or maybe you finally did something you’ve wanted to do your whole life.

I can tell you that all three of those things happened to me, and that’s why I can look back and say I had a decent year. And I bet that if you give it some thought, you can say the same thing.

Share it below, tell us what awesome thing happened to you this year. And use that positivity to attack the new year with an enthusiasm unknown to mankind!

I hope you all have a wonderful New Year’s Eve, and a fucking awesome 2018.

[gettingthesciencewrite]

Bonus Science Fact of the Week

(Because I am procrastinating on studying for my Ph.D...)

Humans have 46 chromosomes, or 23 pairs. Two of those are sex chromosomes (x and y).

Sooooo..... I would like to point out that the reason why humans can create kids is because one parent provides 23 chromosomes, and the other parent provides the other 23 (all packages up nicely in these cells called “gametes”). When you have a human mate with something like an alien, you’re not going to get a viable offspring.

(I mean, that’s even if they parents can mechanically get together! Most likely, with the speciation due to evolving on seperate planets for who-knows-how-long, a human and alien will not have “compatible parts,” so to speak.)

Back to my non-viable kid comment earlier though: what do I mean by that? Well, there are two options if the egg can be fertilized:

1) The egg is fertilized but does not form a viable fetus for a variety of different reasons (or doesn’t even start growing after fertilization).

2) The fertilized egg does make a living fetus (yay!) that can grow, but the child is now sterile.

Number 2 is the more interesting option here, and we need to know why it happens. To be fertile, one must be able to make gametes (the sperm or the egg/oocyte). You can only make gametes through a process called meiosis, and that doesn’t work for you if you don’t have the same chromosome count from each parent.

This is actually the problem with the mule, which is a cross between a donkey and a horse. The mule can grow, but all mule are sterile (they can’t even mate between other miles). That’s because the horse and the donkey have two different chromosome counts. To form your gametes during meiosis, there’s a step called Metaphase I where your chromosomes in pairs line up. Buuuuuuuut, if you got half of your genes from mom (23 human chromosomes) and the other from dad (28 alien chromosomes), the chromosomes don’t line up correctly, causing meiosis to come to a halt.

So, this puts Spock from Star Trek in a new light: maybe he wasn’t shunned just because he was half human, maybe it also had something to do with him being sterile. I mean, that’s an interesting take on a character!

In summary: the likelyhood of naturally occuring human-alien hybrid kids are extremely unlikely, BUT if it does happen, consider making that character sterile. See how they handle it, and how society treats them for it.

Edit: spelling fixes

[juniperpublishersmicrobiology]

Role of Estrogen in Males: An Update

Authored by  NH Balasinor

Keywords

Keywords: Estrogen, male fertility, spermatogenesis

Go to

Mini Review

It has been 75 years since the discovery of estrogen as a hormone. These years have been marked with enormous progress in our understanding towards the working of this hormone and the functions of its receptors. Besides its indispensible role in reproduction, estrogen is involved in most physiological processes like behaviour, appetite, bone formation and wound healing. Although traditionally considered a ‘female’ reproductive hormone, the role of estrogens in males is now well established. Estrogen receptors have been found to localise throughout the male reproductive tract and testis being an important site of estrogen biosynthesis.

Pioneering studies done by groups of Rao et al. [1] and Robaire et al. [2] brought to fore the effects of administration of supra-physiological doses of exogenous estrogen in males. These studies reported a decrease in male fertility and a concomitant suppression of HPT axis due to feedback regulation of estrogen. Thereafter studies done by Hess and coworkers [3] and in our lab [4,5] have further investigated the effects of this hormonal disruption on the seminiferous epithelium. It was noted however that increase in estradiol levels would result in drastic reduction of testosterone and gonadotropin levels hence the effects observed would be a compound effect of all these hormonal perturbations together. At that time, most studies offered indirect evidence for the role of estrogen in spermatogenesis and male reproduction: through estrogen exposure models, presence of ERs and aromatase (the enzyme for estrogen synthesis) in the testes and ER knockout studies. There was a need to delineate the direct role of estrogen and its receptors in testicular and sperm function. Thus, our laboratory sought to selectively activate estrogen signaling through either of its receptors using agonists specific for the two estrogen receptors (ER) a and p. We have observed decreased male fertility and sperm counts without significantly affecting the HPT axis. While ERa is involved in differentiation of round spermatids into elongated spermatids; ERp regulates germ cell apoptosis and sperm release [6,7]. These studies have indicated the putative roles of estrogen receptors in male germ cell maturation and fertility. In agreement with our in vivo agonist models, our ex vivo seminiferous tubule culture studies have further delineated genes related to sperm release that are involved in the processes of actin reorganization are regulated by estrogen via signaling through ERp while those involved inendocytosis are androgenregulated [8]. We have also shown that Arpclb, an ERp regulated protein, plays indispensible role in actin nucleation during sperm release, blood-testis barrier integrity, along with a moonlighting function in germ cell division during spermatogenesis [9].

Despite all these advances there are still gaps in our knowledge and understanding of estrogen receptors working at the fundamental genomic level and the genes they regulate in the testis. We must also bear in mind the heterogeneous population residing in the testis composing of germ cells and somatic cells like Sertoli and Leydig cells, which implies that the ERs may have different genome binding landscapes and functions in these cells. The recent discovery of a membrane bound estrogen receptor, GPER, by Carreau’s group has added a further dimension to the effects of estrogen on the seminiferous epithelium [10]. The importance of understanding the functions of estrogen and its receptors in male reproduction is evident from several studies showing exposure to various endocrine disruptors to be the one causes of declining sperm quality and counts in men over the past 50 years [11]. Many endocrine disruptors found in the environment like organic pesticides DTT and methoxychlor, plasticizers like Bisphenol A, are estrogenic in nature and are reported to cause adverse effects not only on male fertility but also on the reproductive function of the subsequent generations [12].

With technical advancements such as cell type-specific conditional knockdown/knockout, gene editing and high throughput discovery methods like NGS, we are close to understanding direct molecular targets of estrogen and their regulation in a cell-specific context. Such studies are the need of the hour and will bring forth earlier unexplored areas of estrogen function in male reproduction.

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Advances in Biotechnology & Microbiology in Full text in Juniper Publishers

https://juniperpublishers.com/aibm/AIBM.MS.ID.555587.php

[unioncollegeespe]

Split-Sex Animals Are Unusual, Yes, but Not as Rare as You’d Think

Butterfly collectors all can remember their first gynandromorph: a butterfly with a color and pattern that are distinctly male on one wing and female on another. Biologist Nipam H. Patel, the sighting offered a possible answer to his question that he had for years, During embryonic and larval development, how do cells know where to stop and where to go? He was convinced that the delicate black outlines between male and female regions appearing on one wing, but not the other, identified a key facet of animal development. Dr. Patel, heads of the Marine Biological Laboratory said, “It immediately struck me that this was telling me something interesting about how the wing was being made.”

(Top left, a male blue morpho butterfly; top middle, a female. The remainder are gynandromorphic, with both male and female characteristics.)

The patterning on the gynandromorph wing shows that the body uses signaling centers to control where cells go during development and what tissues they become in creatures as diverse as butterflies and people, Patel said. Scientists and measures for centuries have been fascinated by gynandromorph butterflies and other half-male, half-female creatures, particular birds. The latest sensation was a half0red, half-taupe cardinal that became a regular visitor in the backyard of Shirley and Jeffrey Caldwell in Erie, Pa. Its color division strongly suggests that it is a gynandromorph, although the bird would have to be tested to confirm it. It extends beyond birds and butterflies to other insects and crustaceans, like lobsters and crabs.

Split-sex animals and insects could offer clues to why some human diseases strike one sex more than the other. Gynandromorphs suggest that there is more to learn than researchers thought said Jennifer Marshall Graves, a distinguished professor at La Trobe University in Melbourne Australia. She also went on to say that Mammals have X and Y chromosomes, birds and insects have Z and W, and some reptiles can change their sex depending on temperature, or a combination of temp and sex chromosomes. It has been believed that the sex of a bird was determined by a protein made by the DMRT1 gene, which would reach all the cells of the bird through the bloodstream. But for two sides of the bird to share the same bloodstream but not the same sex, there must be more.

Hormones can be the sole drivers of sex either, but they do play some role, Arthur Arnold said, a distinguished research professor at the University of California, Los Angeles. Dr. Arnold showed that in gynandromorphic zebra finches, brain cells on the female side were more masculine than comparable cells in a typical female, showed by Dr. Arnold in a paper published in 2002.

What still remains a mystery is how gynandromorphs are born. For birds, the most likely answer is that a female makes an unusual double nucleus egg cell, one with a Z chromosome and one with a W chromosome, and each is fertilized by a Z sperm, making some cells ZZ and others ZW in the same individual. Dr. Arnold added, “Although this happens regularly, it’s very rare.” Gene editing is tricky in birds, so it has not been possible to experimentally induce this phenomenon in birds, and it's not well understood, he said. The same process is very unlikely to happen in mammals. Female mammals naturally have two of the same sex chromosomes and the instant a mammalian egg and sperm fuse, “dramatic changes prevent the entry of a second sperm.” Gynandromorphs occur naturally, usually resulting from a random genetic error, Dr. Patel said. With some flies and moths passing unstable sex chromosomes down to their offspring, he said. But it is also possible that stress can cause the unusual sex split. Dr. Patel has his scientists use radiation to create gynandromorph flies but it is difficult to sort out the potential causes, including environmental harm, in a wild population. It’s impossible to track an entire population to understand what percentage have unusual sex chromosomes. It still remains unclear why cells of the opposite sex end up on opposite sides of these gynandromorphs. A 2010 study in chickens showed that cells weren’t that evenly distributed; although many of the birds studied have been roughly 50/50 on either side.

Animals can also develop as mosaics, with some cells genetically different from others. Multiple of Patels butterflies show male coloration and patterns on parts of a wing, rather than the entire side.

(from left, a male pamela butterfly, a mosaic gynandromorph and a female)

His own research on sex genes has implications for treating a variety of human diseases that seem to vary by gender said Arnold. Rhonda Voskuhl, Arnold’s U.C.L.A. collaborator found that in multiple sclerosis, a genetically female mouse with two X chromosomes fares worse than a mouse with an X and Y, even if they have the same hormones. It would help treat M.S. in people if we understand why females fare worse, where there is also a gender difference with women accounting for three times as many cases as men. It is also noted that obesity, metabolic syndrome, autoimmune disease, Alzheimer’s, even eating differs by sex. Arnold said that twenty years ago, scientists didn't think that sex chromosomes played any role at all in causing sex differences in thee diseases. “But now we know it makes a difference in mice, so we can say: Where does it make a difference in humans?”

A better understanding of the role of sex in disease would eventually enable better treatments. Arnold said, “That’s kind of the hope ─ that sex differences are not only important to understanding diseases in men and women, but also to developing a more fundamental understanding of the disease processes, so that you can manipulate them.” In most cases, losing a chromosome or having an extra one is lethal, said Jeannie Lee, a geneticist and expert on the X chromosome at Harvard Medical School and Massachusetts General Hospital. 46 chromosomes are within most people, 23 from each parent. Some chromosomes can come with an extra copy, including chromosomes 13, 18 and 21  ─ which is commonly called Down syndrome. Losing any chromosome other than a second sex chromosome is always lethal to a fetus. But the sex chromosome is the only one that people can survive with just one copy, Grave said. “Girls with a single X and no Y suffer few anomalies because the second X is largely inactive anyway. After all, males only have one X.”

(Trisomy 21-Down Syndrome)

People with anomalous numbers of sex chromosomes, such as those with Turner Syndrome, have a  range of problems from virtually no issues to infertility, heart problems and cognitive impairment. Turner Syndrome affects about one in 2,500 girls. It is also possible for people to be intersex, born with reproductive or sexual anatomy that doesn't fit the typical definitions of female or male, which may but doesn't have to involve sex chromosomes, according to the Intersex Society of North America, an advocacy group. Karissa Sanbonmatsu, a structural biologist and principal investigator at Los Alamos National Laboratory in New Mexico says that it is not clear what mechanisms the body has to ensure that most men get only one Y and most women get two X chromosomes. In typical, one X is usually, but no always turned off and some research suggests that there is a mechanism that counts how many X chromosomes are present and generally turns of all but one of them. The interplay between genetics and hormones is complicated, “Genetics produce hormones but then hormones can reprogram DNA” she said, which might explain why there is a mismatch in some people between their sex chromosomes and their sex hormones. People with androgen insensitivity are born with XY chromosomes, but develop as female, because their cells cannot process male hormones. “So, it’s as if the testosterone does not exist,” she said. They are infertile. The more science learns about sex, “the more we find anomalies,” said Alice Dreger, a historian of sexuality. “Nature with conformity all the time in brutal ways and loving ways and all the rest of it,” Dreger said. “It does follow the human fantasy of everybody having to be normal. And humans don't follow that ridiculous idea either.”

https://www.nytimes.com/2019/02/25/science/split-sex-gynandromorph.html

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Scientists Take a Harder Look at Genetic Engineering of Human Embryos

New Post has been published on http://thefaerytale.com/scientists-take-a-harder-look-at-genetic-engineering-of-human-embryos/

Scientists Take a Harder Look at Genetic Engineering of Human Embryos

The distant future of designer babies might not seem so distant after all. The last year has been full of news about genetic engineering—much of it driven by the the cut-and-paste technique called Crispr. And at the top of the list: news that Crispr could modify human embryos, correcting a relatively common, often deadly mutation.

The researcher who spearheaded that work in the US, a controversial cell biologist named Shoukhrat Mitalipov, said not only that his team had used Crispr to correct a mutation in a newly fertilized embryo, but that they’d done it via a mechanism that was, if not novel, at least unusual. The response from the scientific community was immediate and negative. They just kinda didn’t buy it. So Wednesday, in the journal Nature—where Mitalipov published the initial work—two groups of researchers published pointed, acronym- and infographic-filled critiques of Mitalipov’s 2017 paper, and Mitalipov attempted to respond. Because the ethics don’t matter—well, not yet—if the science doesn’t actually work.

You know how babies are made, right? Well, Mitalipov’s team didn’t do it that way. Using existing human embryos for scientific research is mostly a no-no in the US, so the scientists took normal human eggs and fertilized them with sperm containing a mutant version of a gene called MYBPC3. That version underlies a disease called hypertrophic cardiomyopathy, the most common cause of sudden death in young athletes. People with two copies of mutant MYBPC3—one from mom and one from dad, or homologous for the allele, in the language of genetics—rarely survive childhood. People with just one copy—heterozygous—often have heart problems as they get older.

To try to correct the mutation, Mitalipov’s team used Crispr to cut the mutant gene from the paternal chromosomes and then insert a synthetic, corrected version. But that second step didn’t happen. Instead, according to Mitalipov’s analysis, the cell copied the wild type gene from the maternal chromosomes and inserted that instead. The result: embryos with two wild type alleles. It’s called “homology-dependent repair” or “inter-homolog homologous repair.”

“Some of these authors had been studying DNA repair, and somehow they missed this elephant in the room,” says Mitalipov, the director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University. “We’re pointing to a huge gap in knowledge about how genes repair. We’re not sure if it happens in somatic lineages, but in embryonic lineages, we’ve now proved it.”

Embryologists and cell biologists didn’t think they’d missed an elephant. They didn’t think there was one. “We thought there was an alternative interpretation,” says Paul Thomas, director of SA Genome Editing at the South Australian Health and Medical Research Institute and a lead author of one of the critique articles. Thomas’ work has shown that in mice, Crispr tends to cut big chunks of DNA out of the genome, so-called large deletions. He suspects that’s what happened in the Mitalipov embryos, too—they were missing large-deletion failures. “If there’s a large deletion created on the chromosome, you need to look specifically for that event,” Thomas says. “And if you use the assay they used, a pretty standard assay, that won’t detect it.”

It’d be like trying to figure out how many kinds of bagels a bakery makes by counting what’s on the shelf at the end of the day. Your stats would say the bakery mostly makes blueberry, but that’s because the good flavors like poppy seed, garlic, salt, and plain were invisible—bought before you got there. Your count would overestimate blueberry output as a proportion of overall bagelry.

Could this just be a problem of mice and men? Sure. “It’s certainly the case that more and more people are seeing large deletions in mouse embryos. What’s not clear is whether large deletions are occurring in human embryos, because really we only have this study and a handful of others,” Thomas says.

So Mitalipov’s group went back to the lab. They took their old samples and re-ran the assay, a technique called polymerase chain reaction that makes large enough volumes of DNA to sequence and analyze. This time, they looked at a longer stretch of the chromosome. “We did assays with large-scale PCR, up to 10,000 base pairs, and we still didn’t see any deletions,” Mitalipov says. He didn’t expect to find any. His group’s first paper reported a success rate—which is to say, a rate of fixing the mutation—of around 70 percent. Mitalipov says it’s hard to believe that he’d have Crispr-induced large deletions in 70 percent of his embryos. That’d render the technique broadly unusable, he says.

Case not closed, though. “We’re quite surprised they don’t see any evidence of deletions in any of the samples in their response paper,” Thomas says. “We don’t think they’ve fully excluded the possibility.” Fatwa Adikusuma, one of Thomas’ co-authors, suggests a more precise assay like qPCR (which looks at the amount of DNA quantitatively—hence the Q) would work. Mitalipov didn’t try that.

Other teams had other questions. For example, a group led by Dieter Egli of Columbia University and Maria Jasin of Memorial Sloan Kettering Cancer Center (and including the outspoken Harvard biotechnologist George Church) wondered how the Crispr complex could’ve gotten ahold of the maternal wild-type gene, since the mom-contribution and the dad-contribution are separate for the early parts of cell division. Mitalipov says the clusters of parental DNA, contained in envelopes called pronuclei, come into contact with plenty of time for the repair process to work. “If that’s correct, then it’s puzzling that they don’t report more mosaicism in those embryos,” says Paul Knoepfler, a cell biologist at UC Davis. “Mosaicism” is when a single organism has different genomes in different cells. “Crispr acting so late, such as at the two-cell embryo stage, would likely cause variable genetic outcomes,” Knoepfler says—and that could make for less healthy embryos later on.

So is it possible that Mitalipov got it right? “As presented, the new data is consistent with gene correction,” Jasin writes in an email. But, she says, Mitalipov’s own response shows how tough this kind of research is. One of his embryos showed “allele dropout,” when his team couldn’t detect alleles from both parents. “It is uncertain whether gene correction by inter-homolog recombination occurred in all of the embryos, some of the embryos, or, in the most extreme case, none of the embryos,” Jasin adds.

Everyone, including Mitalipov, says it’ll take more research to be sure. That’s fine with him; he understands that people have plenty of concerns about what he says he did. If his method really works, it only works in embryos with one wild-type copy of a gene, for one thing—there has to be a wild type version of the gene for the cell to copy. But more than that, it takes time and work for new ideas to penetrate a field. “There are dogmas, particularly in biology,” Mitalipov says. “And we just bumped in with our result, saying this is an unknown but strong repair pathway in human embryos.”

It’ll certainly take time for that “dogma” to make way for this approach. “Mitalipov’s team has strengthened their case somewhat,” Knoepfler says. “Maybe this is pointing us in the direction of understanding fundamentally new mechanisms in early human embryos, but it’s also possible that a year from now we’ll view this entirely differently.” Either way, for something to get to the clinic, it’ll have to perform better than 70 percent. That means it’s time for more work in the lab.

More Great WIRED Stories

[lazilysillyprince]

Scientists Take a Harder Look at Genetic Engineering of Human Embryos

New Post has been published on http://thefaerytale.com/scientists-take-a-harder-look-at-genetic-engineering-of-human-embryos/

Scientists Take a Harder Look at Genetic Engineering of Human Embryos

The distant future of designer babies might not seem so distant after all. The last year has been full of news about genetic engineering—much of it driven by the the cut-and-paste technique called Crispr. And at the top of the list: news that Crispr could modify human embryos, correcting a relatively common, often deadly mutation.

The researcher who spearheaded that work in the US, a controversial cell biologist named Shoukhrat Mitalipov, said not only that his team had used Crispr to correct a mutation in a newly fertilized embryo, but that they’d done it via a mechanism that was, if not novel, at least unusual. The response from the scientific community was immediate and negative. They just kinda didn’t buy it. So Wednesday, in the journal Nature—where Mitalipov published the initial work—two groups of researchers published pointed, acronym- and infographic-filled critiques of Mitalipov’s 2017 paper, and Mitalipov attempted to respond. Because the ethics don’t matter—well, not yet—if the science doesn’t actually work.

You know how babies are made, right? Well, Mitalipov’s team didn’t do it that way. Using existing human embryos for scientific research is mostly a no-no in the US, so the scientists took normal human eggs and fertilized them with sperm containing a mutant version of a gene called MYBPC3. That version underlies a disease called hypertrophic cardiomyopathy, the most common cause of sudden death in young athletes. People with two copies of mutant MYBPC3—one from mom and one from dad, or homologous for the allele, in the language of genetics—rarely survive childhood. People with just one copy—heterozygous—often have heart problems as they get older.

To try to correct the mutation, Mitalipov’s team used Crispr to cut the mutant gene from the paternal chromosomes and then insert a synthetic, corrected version. But that second step didn’t happen. Instead, according to Mitalipov’s analysis, the cell copied the wild type gene from the maternal chromosomes and inserted that instead. The result: embryos with two wild type alleles. It’s called “homology-dependent repair” or “inter-homolog homologous repair.”

“Some of these authors had been studying DNA repair, and somehow they missed this elephant in the room,” says Mitalipov, the director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University. “We’re pointing to a huge gap in knowledge about how genes repair. We’re not sure if it happens in somatic lineages, but in embryonic lineages, we’ve now proved it.”

Embryologists and cell biologists didn’t think they’d missed an elephant. They didn’t think there was one. “We thought there was an alternative interpretation,” says Paul Thomas, director of SA Genome Editing at the South Australian Health and Medical Research Institute and a lead author of one of the critique articles. Thomas’ work has shown that in mice, Crispr tends to cut big chunks of DNA out of the genome, so-called large deletions. He suspects that’s what happened in the Mitalipov embryos, too—they were missing large-deletion failures. “If there’s a large deletion created on the chromosome, you need to look specifically for that event,” Thomas says. “And if you use the assay they used, a pretty standard assay, that won’t detect it.”

It’d be like trying to figure out how many kinds of bagels a bakery makes by counting what’s on the shelf at the end of the day. Your stats would say the bakery mostly makes blueberry, but that’s because the good flavors like poppy seed, garlic, salt, and plain were invisible—bought before you got there. Your count would overestimate blueberry output as a proportion of overall bagelry.

Could this just be a problem of mice and men? Sure. “It’s certainly the case that more and more people are seeing large deletions in mouse embryos. What’s not clear is whether large deletions are occurring in human embryos, because really we only have this study and a handful of others,” Thomas says.

So Mitalipov’s group went back to the lab. They took their old samples and re-ran the assay, a technique called polymerase chain reaction that makes large enough volumes of DNA to sequence and analyze. This time, they looked at a longer stretch of the chromosome. “We did assays with large-scale PCR, up to 10,000 base pairs, and we still didn’t see any deletions,” Mitalipov says. He didn’t expect to find any. His group’s first paper reported a success rate—which is to say, a rate of fixing the mutation—of around 70 percent. Mitalipov says it’s hard to believe that he’d have Crispr-induced large deletions in 70 percent of his embryos. That’d render the technique broadly unusable, he says.

Case not closed, though. “We’re quite surprised they don’t see any evidence of deletions in any of the samples in their response paper,” Thomas says. “We don’t think they’ve fully excluded the possibility.” Fatwa Adikusuma, one of Thomas’ co-authors, suggests a more precise assay like qPCR (which looks at the amount of DNA quantitatively—hence the Q) would work. Mitalipov didn’t try that.

Other teams had other questions. For example, a group led by Dieter Egli of Columbia University and Maria Jasin of Memorial Sloan Kettering Cancer Center (and including the outspoken Harvard biotechnologist George Church) wondered how the Crispr complex could’ve gotten ahold of the maternal wild-type gene, since the mom-contribution and the dad-contribution are separate for the early parts of cell division. Mitalipov says the clusters of parental DNA, contained in envelopes called pronuclei, come into contact with plenty of time for the repair process to work. “If that’s correct, then it’s puzzling that they don’t report more mosaicism in those embryos,” says Paul Knoepfler, a cell biologist at UC Davis. “Mosaicism” is when a single organism has different genomes in different cells. “Crispr acting so late, such as at the two-cell embryo stage, would likely cause variable genetic outcomes,” Knoepfler says—and that could make for less healthy embryos later on.

So is it possible that Mitalipov got it right? “As presented, the new data is consistent with gene correction,” Jasin writes in an email. But, she says, Mitalipov’s own response shows how tough this kind of research is. One of his embryos showed “allele dropout,” when his team couldn’t detect alleles from both parents. “It is uncertain whether gene correction by inter-homolog recombination occurred in all of the embryos, some of the embryos, or, in the most extreme case, none of the embryos,” Jasin adds.

Everyone, including Mitalipov, says it’ll take more research to be sure. That’s fine with him; he understands that people have plenty of concerns about what he says he did. If his method really works, it only works in embryos with one wild-type copy of a gene, for one thing—there has to be a wild type version of the gene for the cell to copy. But more than that, it takes time and work for new ideas to penetrate a field. “There are dogmas, particularly in biology,” Mitalipov says. “And we just bumped in with our result, saying this is an unknown but strong repair pathway in human embryos.”

It’ll certainly take time for that “dogma” to make way for this approach. “Mitalipov’s team has strengthened their case somewhat,” Knoepfler says. “Maybe this is pointing us in the direction of understanding fundamentally new mechanisms in early human embryos, but it’s also possible that a year from now we’ll view this entirely differently.” Either way, for something to get to the clinic, it’ll have to perform better than 70 percent. That means it’s time for more work in the lab.

More Great WIRED Stories

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Scientists Take a Harder Look at Genetic Engineering of Human Embryos

New Post has been published on http://thefaerytale.com/scientists-take-a-harder-look-at-genetic-engineering-of-human-embryos/

Scientists Take a Harder Look at Genetic Engineering of Human Embryos

The distant future of designer babies might not seem so distant after all. The last year has been full of news about genetic engineering—much of it driven by the the cut-and-paste technique called Crispr. And at the top of the list: news that Crispr could modify human embryos, correcting a relatively common, often deadly mutation.

The researcher who spearheaded that work in the US, a controversial cell biologist named Shoukhrat Mitalipov, said not only that his team had used Crispr to correct a mutation in a newly fertilized embryo, but that they’d done it via a mechanism that was, if not novel, at least unusual. The response from the scientific community was immediate and negative. They just kinda didn’t buy it. So Wednesday, in the journal Nature—where Mitalipov published the initial work—two groups of researchers published pointed, acronym- and infographic-filled critiques of Mitalipov’s 2017 paper, and Mitalipov attempted to respond. Because the ethics don’t matter—well, not yet—if the science doesn’t actually work.

You know how babies are made, right? Well, Mitalipov’s team didn’t do it that way. Using existing human embryos for scientific research is mostly a no-no in the US, so the scientists took normal human eggs and fertilized them with sperm containing a mutant version of a gene called MYBPC3. That version underlies a disease called hypertrophic cardiomyopathy, the most common cause of sudden death in young athletes. People with two copies of mutant MYBPC3—one from mom and one from dad, or homologous for the allele, in the language of genetics—rarely survive childhood. People with just one copy—heterozygous—often have heart problems as they get older.

To try to correct the mutation, Mitalipov’s team used Crispr to cut the mutant gene from the paternal chromosomes and then insert a synthetic, corrected version. But that second step didn’t happen. Instead, according to Mitalipov’s analysis, the cell copied the wild type gene from the maternal chromosomes and inserted that instead. The result: embryos with two wild type alleles. It’s called “homology-dependent repair” or “inter-homolog homologous repair.”

“Some of these authors had been studying DNA repair, and somehow they missed this elephant in the room,” says Mitalipov, the director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University. “We’re pointing to a huge gap in knowledge about how genes repair. We’re not sure if it happens in somatic lineages, but in embryonic lineages, we’ve now proved it.”

Embryologists and cell biologists didn’t think they’d missed an elephant. They didn’t think there was one. “We thought there was an alternative interpretation,” says Paul Thomas, director of SA Genome Editing at the South Australian Health and Medical Research Institute and a lead author of one of the critique articles. Thomas’ work has shown that in mice, Crispr tends to cut big chunks of DNA out of the genome, so-called large deletions. He suspects that’s what happened in the Mitalipov embryos, too—they were missing large-deletion failures. “If there’s a large deletion created on the chromosome, you need to look specifically for that event,” Thomas says. “And if you use the assay they used, a pretty standard assay, that won’t detect it.”

It’d be like trying to figure out how many kinds of bagels a bakery makes by counting what’s on the shelf at the end of the day. Your stats would say the bakery mostly makes blueberry, but that’s because the good flavors like poppy seed, garlic, salt, and plain were invisible—bought before you got there. Your count would overestimate blueberry output as a proportion of overall bagelry.

Could this just be a problem of mice and men? Sure. “It’s certainly the case that more and more people are seeing large deletions in mouse embryos. What’s not clear is whether large deletions are occurring in human embryos, because really we only have this study and a handful of others,” Thomas says.

So Mitalipov’s group went back to the lab. They took their old samples and re-ran the assay, a technique called polymerase chain reaction that makes large enough volumes of DNA to sequence and analyze. This time, they looked at a longer stretch of the chromosome. “We did assays with large-scale PCR, up to 10,000 base pairs, and we still didn’t see any deletions,” Mitalipov says. He didn’t expect to find any. His group’s first paper reported a success rate—which is to say, a rate of fixing the mutation—of around 70 percent. Mitalipov says it’s hard to believe that he’d have Crispr-induced large deletions in 70 percent of his embryos. That’d render the technique broadly unusable, he says.

Case not closed, though. “We’re quite surprised they don’t see any evidence of deletions in any of the samples in their response paper,” Thomas says. “We don’t think they’ve fully excluded the possibility.” Fatwa Adikusuma, one of Thomas’ co-authors, suggests a more precise assay like qPCR (which looks at the amount of DNA quantitatively—hence the Q) would work. Mitalipov didn’t try that.

Other teams had other questions. For example, a group led by Dieter Egli of Columbia University and Maria Jasin of Memorial Sloan Kettering Cancer Center (and including the outspoken Harvard biotechnologist George Church) wondered how the Crispr complex could’ve gotten ahold of the maternal wild-type gene, since the mom-contribution and the dad-contribution are separate for the early parts of cell division. Mitalipov says the clusters of parental DNA, contained in envelopes called pronuclei, come into contact with plenty of time for the repair process to work. “If that’s correct, then it’s puzzling that they don’t report more mosaicism in those embryos,” says Paul Knoepfler, a cell biologist at UC Davis. “Mosaicism” is when a single organism has different genomes in different cells. “Crispr acting so late, such as at the two-cell embryo stage, would likely cause variable genetic outcomes,” Knoepfler says—and that could make for less healthy embryos later on.

So is it possible that Mitalipov got it right? “As presented, the new data is consistent with gene correction,” Jasin writes in an email. But, she says, Mitalipov’s own response shows how tough this kind of research is. One of his embryos showed “allele dropout,” when his team couldn’t detect alleles from both parents. “It is uncertain whether gene correction by inter-homolog recombination occurred in all of the embryos, some of the embryos, or, in the most extreme case, none of the embryos,” Jasin adds.

Everyone, including Mitalipov, says it’ll take more research to be sure. That’s fine with him; he understands that people have plenty of concerns about what he says he did. If his method really works, it only works in embryos with one wild-type copy of a gene, for one thing—there has to be a wild type version of the gene for the cell to copy. But more than that, it takes time and work for new ideas to penetrate a field. “There are dogmas, particularly in biology,” Mitalipov says. “And we just bumped in with our result, saying this is an unknown but strong repair pathway in human embryos.”

It’ll certainly take time for that “dogma” to make way for this approach. “Mitalipov’s team has strengthened their case somewhat,” Knoepfler says. “Maybe this is pointing us in the direction of understanding fundamentally new mechanisms in early human embryos, but it’s also possible that a year from now we’ll view this entirely differently.” Either way, for something to get to the clinic, it’ll have to perform better than 70 percent. That means it’s time for more work in the lab.

More Great WIRED Stories

[awesomecolorfulcollectorwombat]

Scientists Take a Harder Look at Genetic Engineering of Human Embryos

New Post has been published on http://thefaerytale.com/scientists-take-a-harder-look-at-genetic-engineering-of-human-embryos/

Scientists Take a Harder Look at Genetic Engineering of Human Embryos

The distant future of designer babies might not seem so distant after all. The last year has been full of news about genetic engineering—much of it driven by the the cut-and-paste technique called Crispr. And at the top of the list: news that Crispr could modify human embryos, correcting a relatively common, often deadly mutation.

The researcher who spearheaded that work in the US, a controversial cell biologist named Shoukhrat Mitalipov, said not only that his team had used Crispr to correct a mutation in a newly fertilized embryo, but that they’d done it via a mechanism that was, if not novel, at least unusual. The response from the scientific community was immediate and negative. They just kinda didn’t buy it. So Wednesday, in the journal Nature—where Mitalipov published the initial work—two groups of researchers published pointed, acronym- and infographic-filled critiques of Mitalipov’s 2017 paper, and Mitalipov attempted to respond. Because the ethics don’t matter—well, not yet—if the science doesn’t actually work.

You know how babies are made, right? Well, Mitalipov’s team didn’t do it that way. Using existing human embryos for scientific research is mostly a no-no in the US, so the scientists took normal human eggs and fertilized them with sperm containing a mutant version of a gene called MYBPC3. That version underlies a disease called hypertrophic cardiomyopathy, the most common cause of sudden death in young athletes. People with two copies of mutant MYBPC3—one from mom and one from dad, or homologous for the allele, in the language of genetics—rarely survive childhood. People with just one copy—heterozygous—often have heart problems as they get older.

To try to correct the mutation, Mitalipov’s team used Crispr to cut the mutant gene from the paternal chromosomes and then insert a synthetic, corrected version. But that second step didn’t happen. Instead, according to Mitalipov’s analysis, the cell copied the wild type gene from the maternal chromosomes and inserted that instead. The result: embryos with two wild type alleles. It’s called “homology-dependent repair” or “inter-homolog homologous repair.”

“Some of these authors had been studying DNA repair, and somehow they missed this elephant in the room,” says Mitalipov, the director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University. “We’re pointing to a huge gap in knowledge about how genes repair. We’re not sure if it happens in somatic lineages, but in embryonic lineages, we’ve now proved it.”

Embryologists and cell biologists didn’t think they’d missed an elephant. They didn’t think there was one. “We thought there was an alternative interpretation,” says Paul Thomas, director of SA Genome Editing at the South Australian Health and Medical Research Institute and a lead author of one of the critique articles. Thomas’ work has shown that in mice, Crispr tends to cut big chunks of DNA out of the genome, so-called large deletions. He suspects that’s what happened in the Mitalipov embryos, too—they were missing large-deletion failures. “If there’s a large deletion created on the chromosome, you need to look specifically for that event,” Thomas says. “And if you use the assay they used, a pretty standard assay, that won’t detect it.”

It’d be like trying to figure out how many kinds of bagels a bakery makes by counting what’s on the shelf at the end of the day. Your stats would say the bakery mostly makes blueberry, but that’s because the good flavors like poppy seed, garlic, salt, and plain were invisible—bought before you got there. Your count would overestimate blueberry output as a proportion of overall bagelry.

Could this just be a problem of mice and men? Sure. “It’s certainly the case that more and more people are seeing large deletions in mouse embryos. What’s not clear is whether large deletions are occurring in human embryos, because really we only have this study and a handful of others,” Thomas says.

So Mitalipov’s group went back to the lab. They took their old samples and re-ran the assay, a technique called polymerase chain reaction that makes large enough volumes of DNA to sequence and analyze. This time, they looked at a longer stretch of the chromosome. “We did assays with large-scale PCR, up to 10,000 base pairs, and we still didn’t see any deletions,” Mitalipov says. He didn’t expect to find any. His group’s first paper reported a success rate—which is to say, a rate of fixing the mutation—of around 70 percent. Mitalipov says it’s hard to believe that he’d have Crispr-induced large deletions in 70 percent of his embryos. That’d render the technique broadly unusable, he says.

Case not closed, though. “We’re quite surprised they don’t see any evidence of deletions in any of the samples in their response paper,” Thomas says. “We don’t think they’ve fully excluded the possibility.” Fatwa Adikusuma, one of Thomas’ co-authors, suggests a more precise assay like qPCR (which looks at the amount of DNA quantitatively—hence the Q) would work. Mitalipov didn’t try that.

Other teams had other questions. For example, a group led by Dieter Egli of Columbia University and Maria Jasin of Memorial Sloan Kettering Cancer Center (and including the outspoken Harvard biotechnologist George Church) wondered how the Crispr complex could’ve gotten ahold of the maternal wild-type gene, since the mom-contribution and the dad-contribution are separate for the early parts of cell division. Mitalipov says the clusters of parental DNA, contained in envelopes called pronuclei, come into contact with plenty of time for the repair process to work. “If that’s correct, then it’s puzzling that they don’t report more mosaicism in those embryos,” says Paul Knoepfler, a cell biologist at UC Davis. “Mosaicism” is when a single organism has different genomes in different cells. “Crispr acting so late, such as at the two-cell embryo stage, would likely cause variable genetic outcomes,” Knoepfler says—and that could make for less healthy embryos later on.

So is it possible that Mitalipov got it right? “As presented, the new data is consistent with gene correction,” Jasin writes in an email. But, she says, Mitalipov’s own response shows how tough this kind of research is. One of his embryos showed “allele dropout,” when his team couldn’t detect alleles from both parents. “It is uncertain whether gene correction by inter-homolog recombination occurred in all of the embryos, some of the embryos, or, in the most extreme case, none of the embryos,” Jasin adds.

Everyone, including Mitalipov, says it’ll take more research to be sure. That’s fine with him; he understands that people have plenty of concerns about what he says he did. If his method really works, it only works in embryos with one wild-type copy of a gene, for one thing—there has to be a wild type version of the gene for the cell to copy. But more than that, it takes time and work for new ideas to penetrate a field. “There are dogmas, particularly in biology,” Mitalipov says. “And we just bumped in with our result, saying this is an unknown but strong repair pathway in human embryos.”

It’ll certainly take time for that “dogma” to make way for this approach. “Mitalipov’s team has strengthened their case somewhat,” Knoepfler says. “Maybe this is pointing us in the direction of understanding fundamentally new mechanisms in early human embryos, but it’s also possible that a year from now we’ll view this entirely differently.” Either way, for something to get to the clinic, it’ll have to perform better than 70 percent. That means it’s time for more work in the lab.

More Great WIRED Stories

[ivf-meds]

IVF doesn’t cause low sperm counts in boy babies—they inherit it

The chicken and the egg metaphor might be too apt. A new study shows that the sons of men who conceived using an in vitro fertilization (IVF) procedure grow up to be men with low sperm counts who may eventually need to use that same procedure. The study generated a lot of buzz with several mainstream outlets publishing stories about the study, unfortunately for men, not many got it right. The coverage of the story makes it clear that many are still confused about what IVF and similar treatments do to help couples conceive.

Fertility experts at University Hospital Brussels first developed the technique called intracytoplasmic sperm injection (ICSI) in the early 90s. ICSI is ideal for men with low sperm counts or poor motility. These are men who already have issues with their sperm—but the treatment doesn’t fix their problems. Sperm motility is vital for conception because the sperm must swim through portions of the female reproductive tract to reach the egg. ICSI merely does the work for their sperm—it’s like picking up a small child to help them dunk a basketball. In this process, a woman undergoes hormone treatment and egg harvesting. Then, under a microscope, a single sperm is injected into the egg to fertilize it before the embryo is implanted in the woman’s uterus.

That same research group tracked down 54 boys conceived using the technique and compared their sperm count, motility, and shape to age-matched controls who were conceived naturally. The ICSI-conceived men had half the concentration of sperm as naturally conceived men, a little more than half the sperm count and 66 percent lower motility.

But these results shouldn’t really surprise anyone. Fertility problems that cause drastic reductions in sperm quality and quantity are thought to be genetically based. All the results show is that dad’s with fertility problems—had sons with fertility problems. Study author and ICSI pioneer Andre Van Steirteghem told the press:

These first results from the oldest group of ICSI-conceived adults worldwide indicate that a degree of ���sub-fertility’ has, indeed, been passed on to sons of fathers who underwent ICSI because of impaired semen characteristics.

Some of the reporting about the study suggests that some view IVF and other assisted reproductive technologies as a ‘cure’ for infertility. Here’s what Hannah Devlin wrote in The Guardian (emphasis added):

ICSI is normally used to help couples conceive when the man has a low sperm count, or where there are abnormalities in the shape or movement of the sperm. The latest findings suggest that these problems tend to be passed on to the next generation – there is no suggestion that they are caused by the technique itself.

But these techniques are not promised as a cure for infertility. It’s much better to think of assisted reproduction as a costly workaround for the problems at hand much like an insulin pump assists people with diabetes in controlling the disease but does not cure or treat the underlying condition.

Other outlets focused on the painted a misleading picture: If we keep using technologies to help sub-fertile people reproduce knowing their children are likely to have the same issues will we replace natural conception all together? From Medical Daily:

These results suggest ICSI is not exactly a treatment for male infertility, but rather a way to get through a problem that the next generation will have to deal with. Previous research has estimated if even half of affected men used ICSI to have kids, the incidence of severe male factor infertility could double nationwide within seven generations… This could potentially lead to a society of men who can’t conceive children naturally.

Although IVF has become a well-established procedure since it was pioneered 40 years ago, it still draws controversy. Early this year University of California San Diego evolutionary biologist Pascal Gagneux called it a massive social experiment:

…We’re engaging in an evolutionary experiment … I would compare it to high fructose corn syrup and fast food in the US. It took 50 years; it was fantastic, you got bigger and healthier, and now the US are the first generation that are shorter and heavier and die younger. But it took 50 years…

But correlation-not-causation works in another way, too. The study showed that these ICSI-conceived men had low sperm counts. But that doesn’t guarantee they can’t conceive:

Prof Simon Fishel, Managing Director of CARE Fertility, added: “We may still find that these men are able to conceive naturally “Just having low semen parameters is not evidence for the requirement of ICSI or IVF technologies. We know many men with such are indeed able to conceive naturally.”

That’s pretty common. There are many mysteries of male reproduction, as for years the fertility industry has mainly thought of a couple’s inability to conceive was a ‘female problem.’ But that thinking we know now is incorrect as at least in 40 percent of couples who can’t conceive the sole problem is with the man’s sperm. IVF is often the only answer. Usha Lee McFraling at STAT discussed the issues which come down even to a fundamental lack of biometrics to describe it:

“How many sperm do you have and how well do they swim? That’s been the gold standard forever,” said Richard Scott a fertility expert in New Jersey. “Unfortunately, that’s a very unsophisticated view of a very complex problem.” For example, many men with a low sperm count, or sperm that are misshapen, are able to conceive. And many men with seemingly normal tests results aren’t. “We need much more powerful insights into this process.”

Currently, all we tell men who are struggling to conceive is that they should lose weight and stop smoking to benefit sperm health. But since the problem may be largely genetic–the future of male fertility treatments could be gene editing.

Meredith Knight is a contributor to the human genetics section for Genetic Literacy Project and a freelance science and health writer in Austin, Texas. Follow her @meremereknight. 

Read Article Here- http://ift.tt/2eMDmsh

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from IVF doesn’t cause low sperm counts in boy babies—they inherit it

[kathleenseiber]

Gene makes plants produce less pollen

New research identifies a gene that reduces the amount of pollen that a plant produces.

In the 19th century, Charles Darwin recognized that the number of male gametes—pollen for plants, sperm for animals—is highly variable among individuals and species.

At first sight a high number of male gametes seems beneficial for the competition among males to produce more offspring. However, many domesticated species have a reduced number of male gametes. In theory it might be advantageous to reduce the cost of producing male gametes, for example when the rate of self-fertilization or inbreeding is high and fewer male gametes are necessary for successful reproduction.

“So far there has been little evidence to support this idea, because the production of male gametes is a complex trait affected by many genes with small effects and its molecular basis remained unknown,” says study leader Kentaro Shimizu, professor of evolutionary biology and environmental studies at the University of Zurich.

The new study, published in Nature Communications, provides such evidence and demonstrates that a reduction in pollen number is not necessarily deleterious but rather advantageous in a self-fertilizing species.

Matured anthers of Arabidopsis thaliana: Compared to the wild type (left), the rdp1 mutant (right) contains only half as many pollen grains (in magenta). (Credit: Hiroyuki Kakui)

Grains per flower

For their investigation the researchers used the well-characterized model plant Arabidopsis thaliana that is mainly self-fertilizing and has a reduced number of pollen grains compared to its relatives in the wild. They counted the pollen number of 144 plants with distinct genetic background and found variations from 2,000 to 8,000 pollen grains per flower. They then compared the entire genetic information of these variants, looking for differences between plants with higher and lower pollen numbers.

This computational analysis, a so-called genome-wide association study, revealed one gene that affects the number of pollen each plant produces, which was subsequently named REDUCED POLLEN NUMBER1 (RDP1) gene. Using the novel genome editing technology CRISPR-Cas9 the researchers created several mutant variants of the RDP1 gene, both in plants with high and low pollen number. They crossed the mutated plants with each other and counted the pollen the hybrid offspring produced.

“These experiments confirmed the subtle but significant effect of the RDP1 gene,” says coauthor Misako Yamazaki, a member of the technical staff of the Shimizu group. A comparison with other organisms revealed that the gene encodes a factor that promotes the building of ribosomes, the cellular factories for protein production.

Reproductive success

Next, the team investigated if the reduction in pollen number is positively selected for and did not happen incidentally. For this they used a statistical method to gain insight into the evolution of the RDP1 gene within model plants with different pollen production. The results show that the trait for reduced pollen number has indeed been under positive selection.

Furthermore, the research team studied the evolution of the many genomic regions associated with pollen number. The selection on pollen number was very strong—in comparison to previous studies of more than 100 traits such as disease-resistance and environmental responses. This supports the importance of pollen number for reproductive success.

“The evidence supports the theoretical prediction that reduced investment in male gametes is advantageous. This is not only important for evolutionary biology but also for the practice of plant breeding and domestication in general,” explains Shimizu.

“Many crop plants have a reduced number of pollen due to domestication. Lowering the cost of producing pollen may increase crop yield. On the other hand, too few pollen grains might be an obstacle to breeding and seed production. Our study opens the way for molecular breeding of the optimal pollen number.”

Funding for the study came from the Swiss National Science Foundation, the University of Zurich, and the Japan Science and Technology Agency.

Source: University of Zurich

The post Gene makes plants produce less pollen appeared first on Futurity.

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[fishermariawo]

Dear Mark: Saunas and Finnish Longevity, Saunas and Sperm, What About Ambient Temperature?

For today’s edition of Dear Mark, I’m answering three questions from readers. There was some good feedback after last week’s sauna post, and I want to address a few of the comments. First, does the fact that Finns don’t live as long as some of the other more storied “blue zone” populations despite using saunas negate the utility of the sauna? Second, what should we make of the recent study showing negative effects of sauna on sperm health? And third, isn’t it more “natural” and Primal to seek out smaller ambient temperature fluctuations, rather than brief exposures to extreme temperatures?

Let’s go:

Lots of Finnish references but the Fins are not one of the Blue Zone populations. Of the 5 BZ populations, the Okinawans may use a sauna/hot springs – not sure about the the other 4 though.

Finnish men do have the lowest life expectancy among Nordic countries. It’s still pretty good globally—84 years for women, 79 for men—but for being in one of the more developed areas of the world, it’s not great. Yet they use saunas, a supposedly life-extending practice. What gives?

The biggest killers of Finnish men are diabetes, heart disease, and alcohol. Some combination of diet, genes, environment, and lifestyle are contributing to those deaths—that’s what the Finns are up against. Most of the Blue Zones don’t have these issues:

They tend to be in milder climates with better access to sunshine.

They have lower levels of social isolation than Nordic countries like Finland.

They have more “longevity genes” than other areas. The Blue Zone Sardinians, for example, are the subjects of a major ongoing study into the genetics of longevity.

To say nothing of the diet differences.

Sauna usage may very well be keeping life expectancy higher than it should be, given the other risk factors. Research indicates that using a sauna 4-7 times per week confers a 40% reduction in all-cause mortality and even greater reductions in heart related deaths among middle aged Finnish men, which is the cohort most at risk of dying. These numbers, coupled with the numerous protective mechanisms outlined in the last sauna post, lead me to believe that saunas are helping, not hurting Finnish mortality.

Stefan pointed out:

One conundrum is that daily sauna use will sabotage your ballsack precisely because of the heat. Check this old nut-of-a-study: https://ift.tt/2oC5ofi

Sadly, yes. This is a real issue.

What happened in this study?

10 men were recruited to participate. They were in their 30s, generally healthy, and, at baseline, had normal sperm parameters. For 3 months, they each used the sauna at 80-90?C twice a week for 15 minutes per session. Sperm parameters were tested at the start of the sauna use, after 3 months of sauna, and at 3- and 6-months post sauna. They included:

Sex hormones (testosterone, estradiol, FSH, LH, sex hormone binding globulin)

Sperm count (absolute number of sperm)

Sperm motility (ability of sperm to move independently and perform necessary functions)

Sperm histone/protamine ratios (indicative of sperm quality; smokers’ sperm more likely to have dysfunctional ratio, for example)

Sperm mitochondrial function

After three months of sauna, almost every parameter was negatively affected. Sex hormones remained the same, but sperm count and motility were greatly reduced. The proportion of sperm with dysfunctional histone/protamine ratios increased. Sauna increased the number of sperm with poor mitochondrial function. Luckily, everything returned to normal 6 months after sauna use stopped. But still, that’s a big effect.

This seems like a strong mark against using saunas when you’re trying to conceive. The doses were realistic (15 minutes a day, twice a week) and the effects significant. Not only do saunas appear to lower sperm count and motility, they may decrease the genetic fitness and quality of the surviving sperm. This could increase the risk of miscarriage and even have long term effects on the offspring,

If you’re an older guy uninterested in conceiving, this study shouldn’t affect your sauna habits. Sauna doesn’t affect your sex hormones, which have an outsized effect on the quality of your life. It just reduces the viability of your sperm.

If you’re a younger guy interested in having kids, don’t ignore these results. Avoiding saunas for 3-6 months before trying to conceive might be a good idea.

So, in the name of being seasonal and living naturally, what about just getting out in the heat (and not having an air conditioner–but yet cooking a lot) in the summer and being out in the cold in the winter and keeping the house temp low? Is that enough heat/cold exposure to have beneficial effects? (Might be harder to study.) Instead of taking the time to do something extra that takes up natural resources to create, get the exposure through living. Spend half the year hot and half the year cold. (Plus the cold exposure of going to the grocery store in hardly any clothes in the summer, and the heat exposure of going to someone’s house or the local school dressed for cold in the winter.) (Of course this only works in places that have different weather in the seasons.) Isn’t that more along the lines of Grok-ness?

This is ideal, yes. It’s a great point.

There’s actually some evidence that exposing oneself to cold and hot ambient temperatures, rather than maintaining a steady 70º at all times, is good for us.

As I pointed out in an older post, the general trend is that the more people are exposed to predictable, constant ambient temperatures through central heating, the more likely they are to gain weight. In mice, keeping all other variables (diet, activity, etc) the same while switching to a “thermoneutral” ambient temperature (the temperature at which organisms can maintain body temperature without expending any extra energy) triggered inflammation, increased atherosclerosis, ruined blood lipids, and made the mice obese.

Mild cold exposure (just a few degrees’ worth) was enough to activate brown fat (the metabolically active form that kicks in to keep us warm, burning calories in the process) in people. They achieved it by setting the thermostat a bit lower than normal—nothing extreme like ice baths.

I see saunas and cold baths as extreme stressors that address extreme deficiencies. Just like intense workouts can mitigate the effects of sitting around all the time and failing to get the constant low-level movement our physiologies expect, intense heat or cold exposure can mitigate the effects of indoor climate control. But they’re probably not enough. It’s probably better—and certainly more Primal—to also keep the heat down in the house, walk around in the cold in short sleeves, and get comfortable with hot weather.

One thing I’ve been experimenting with is limiting the amount of time I use the AC. I’m trying to just deal with hot days, whether by walking around in as little clothing as possible or creating air flow with open doors and windows. AC has always felt”stale” and “artificial.” I still use it when it’s unavoidable, but I’m beginning to almost enjoy the sensation of low level heat.

That’s it for today, folks. What’s your take on all this? Anyone conceive despite using the sauna? Anyone else trying to vary the ambient temperature in their life? Let me know down below.

Thanks for reading!

Tanskanen J, Anttila T. A Prospective Study of Social Isolation, Loneliness, and Mortality in Finland. Am J Public Health. 2016;106(11):2042-2048.

Laukkanen T, Khan H, Zaccardi F, Laukkanen JA. Association between sauna bathing and fatal cardiovascular and all-cause mortality events. JAMA Intern Med. 2015;175(4):542-8.

Garolla A, Torino M, Sartini B, et al. Seminal and molecular evidence that sauna exposure affects human spermatogenesis. Hum Reprod. 2013;28(4):877-85.

Giles DA, Ramkhelawon B, Donelan EM, et al. Modulation of ambient temperature promotes inflammation and initiates atherosclerosis in wild type C57BL/6 mice. Mol Metab. 2016;5(11):1121-1130.

Chen KY, Brychta RJ, Linderman JD, et al. Brown fat activation mediates cold-induced thermogenesis in adult humans in response to a mild decrease in ambient temperature. J Clin Endocrinol Metab. 2013;98(7):E1218-23.

[watsonrodriquezie]

Dear Mark: Saunas and Finnish Longevity, Saunas and Sperm, What About Ambient Temperature?

For today’s edition of Dear Mark, I’m answering three questions from readers. There was some good feedback after last week’s sauna post, and I want to address a few of the comments. First, does the fact that Finns don’t live as long as some of the other more storied “blue zone” populations despite using saunas negate the utility of the sauna? Second, what should we make of the recent study showing negative effects of sauna on sperm health? And third, isn’t it more “natural” and Primal to seek out smaller ambient temperature fluctuations, rather than brief exposures to extreme temperatures?

Let’s go:

Lots of Finnish references but the Fins are not one of the Blue Zone populations. Of the 5 BZ populations, the Okinawans may use a sauna/hot springs – not sure about the the other 4 though.

Finnish men do have the lowest life expectancy among Nordic countries. It’s still pretty good globally—84 years for women, 79 for men—but for being in one of the more developed areas of the world, it’s not great. Yet they use saunas, a supposedly life-extending practice. What gives?

The biggest killers of Finnish men are diabetes, heart disease, and alcohol. Some combination of diet, genes, environment, and lifestyle are contributing to those deaths—that’s what the Finns are up against. Most of the Blue Zones don’t have these issues:

They tend to be in milder climates with better access to sunshine.

They have lower levels of social isolation than Nordic countries like Finland.

They have more “longevity genes” than other areas. The Blue Zone Sardinians, for example, are the subjects of a major ongoing study into the genetics of longevity.

To say nothing of the diet differences.

Sauna usage may very well be keeping life expectancy higher than it should be, given the other risk factors. Research indicates that using a sauna 4-7 times per week confers a 40% reduction in all-cause mortality and even greater reductions in heart related deaths among middle aged Finnish men, which is the cohort most at risk of dying. These numbers, coupled with the numerous protective mechanisms outlined in the last sauna post, lead me to believe that saunas are helping, not hurting Finnish mortality.

Stefan pointed out:

One conundrum is that daily sauna use will sabotage your ballsack precisely because of the heat. Check this old nut-of-a-study: https://ift.tt/2oC5ofi

Sadly, yes. This is a real issue.

What happened in this study?

10 men were recruited to participate. They were in their 30s, generally healthy, and, at baseline, had normal sperm parameters. For 3 months, they each used the sauna at 80-90?C twice a week for 15 minutes per session. Sperm parameters were tested at the start of the sauna use, after 3 months of sauna, and at 3- and 6-months post sauna. They included:

Sex hormones (testosterone, estradiol, FSH, LH, sex hormone binding globulin)

Sperm count (absolute number of sperm)

Sperm motility (ability of sperm to move independently and perform necessary functions)

Sperm histone/protamine ratios (indicative of sperm quality; smokers’ sperm more likely to have dysfunctional ratio, for example)

Sperm mitochondrial function

After three months of sauna, almost every parameter was negatively affected. Sex hormones remained the same, but sperm count and motility were greatly reduced. The proportion of sperm with dysfunctional histone/protamine ratios increased. Sauna increased the number of sperm with poor mitochondrial function. Luckily, everything returned to normal 6 months after sauna use stopped. But still, that’s a big effect.

This seems like a strong mark against using saunas when you’re trying to conceive. The doses were realistic (15 minutes a day, twice a week) and the effects significant. Not only do saunas appear to lower sperm count and motility, they may decrease the genetic fitness and quality of the surviving sperm. This could increase the risk of miscarriage and even have long term effects on the offspring,

If you’re an older guy uninterested in conceiving, this study shouldn’t affect your sauna habits. Sauna doesn’t affect your sex hormones, which have an outsized effect on the quality of your life. It just reduces the viability of your sperm.

If you’re a younger guy interested in having kids, don’t ignore these results. Avoiding saunas for 3-6 months before trying to conceive might be a good idea.

So, in the name of being seasonal and living naturally, what about just getting out in the heat (and not having an air conditioner–but yet cooking a lot) in the summer and being out in the cold in the winter and keeping the house temp low? Is that enough heat/cold exposure to have beneficial effects? (Might be harder to study.) Instead of taking the time to do something extra that takes up natural resources to create, get the exposure through living. Spend half the year hot and half the year cold. (Plus the cold exposure of going to the grocery store in hardly any clothes in the summer, and the heat exposure of going to someone’s house or the local school dressed for cold in the winter.) (Of course this only works in places that have different weather in the seasons.) Isn’t that more along the lines of Grok-ness?

This is ideal, yes. It’s a great point.

There’s actually some evidence that exposing oneself to cold and hot ambient temperatures, rather than maintaining a steady 70º at all times, is good for us.

As I pointed out in an older post, the general trend is that the more people are exposed to predictable, constant ambient temperatures through central heating, the more likely they are to gain weight. In mice, keeping all other variables (diet, activity, etc) the same while switching to a “thermoneutral” ambient temperature (the temperature at which organisms can maintain body temperature without expending any extra energy) triggered inflammation, increased atherosclerosis, ruined blood lipids, and made the mice obese.

Mild cold exposure (just a few degrees’ worth) was enough to activate brown fat (the metabolically active form that kicks in to keep us warm, burning calories in the process) in people. They achieved it by setting the thermostat a bit lower than normal—nothing extreme like ice baths.

I see saunas and cold baths as extreme stressors that address extreme deficiencies. Just like intense workouts can mitigate the effects of sitting around all the time and failing to get the constant low-level movement our physiologies expect, intense heat or cold exposure can mitigate the effects of indoor climate control. But they’re probably not enough. It’s probably better—and certainly more Primal—to also keep the heat down in the house, walk around in the cold in short sleeves, and get comfortable with hot weather.

One thing I’ve been experimenting with is limiting the amount of time I use the AC. I’m trying to just deal with hot days, whether by walking around in as little clothing as possible or creating air flow with open doors and windows. AC has always felt”stale” and “artificial.” I still use it when it’s unavoidable, but I’m beginning to almost enjoy the sensation of low level heat.

That’s it for today, folks. What’s your take on all this? Anyone conceive despite using the sauna? Anyone else trying to vary the ambient temperature in their life? Let me know down below.

Thanks for reading!

Tanskanen J, Anttila T. A Prospective Study of Social Isolation, Loneliness, and Mortality in Finland. Am J Public Health. 2016;106(11):2042-2048.

Laukkanen T, Khan H, Zaccardi F, Laukkanen JA. Association between sauna bathing and fatal cardiovascular and all-cause mortality events. JAMA Intern Med. 2015;175(4):542-8.

Garolla A, Torino M, Sartini B, et al. Seminal and molecular evidence that sauna exposure affects human spermatogenesis. Hum Reprod. 2013;28(4):877-85.

Giles DA, Ramkhelawon B, Donelan EM, et al. Modulation of ambient temperature promotes inflammation and initiates atherosclerosis in wild type C57BL/6 mice. Mol Metab. 2016;5(11):1121-1130.

Chen KY, Brychta RJ, Linderman JD, et al. Brown fat activation mediates cold-induced thermogenesis in adult humans in response to a mild decrease in ambient temperature. J Clin Endocrinol Metab. 2013;98(7):E1218-23.

[cynthiamwashington]

Dear Mark: Saunas and Finnish Longevity, Saunas and Sperm, What About Ambient Temperature?

For today’s edition of Dear Mark, I’m answering three questions from readers. There was some good feedback after last week’s sauna post, and I want to address a few of the comments. First, does the fact that Finns don’t live as long as some of the other more storied “blue zone” populations despite using saunas negate the utility of the sauna? Second, what should we make of the recent study showing negative effects of sauna on sperm health? And third, isn’t it more “natural” and Primal to seek out smaller ambient temperature fluctuations, rather than brief exposures to extreme temperatures?

Let’s go:

Lots of Finnish references but the Fins are not one of the Blue Zone populations. Of the 5 BZ populations, the Okinawans may use a sauna/hot springs – not sure about the the other 4 though.

Finnish men do have the lowest life expectancy among Nordic countries. It’s still pretty good globally—84 years for women, 79 for men—but for being in one of the more developed areas of the world, it’s not great. Yet they use saunas, a supposedly life-extending practice. What gives?

The biggest killers of Finnish men are diabetes, heart disease, and alcohol. Some combination of diet, genes, environment, and lifestyle are contributing to those deaths—that’s what the Finns are up against. Most of the Blue Zones don’t have these issues:

They tend to be in milder climates with better access to sunshine.

They have lower levels of social isolation than Nordic countries like Finland.

They have more “longevity genes” than other areas. The Blue Zone Sardinians, for example, are the subjects of a major ongoing study into the genetics of longevity.

To say nothing of the diet differences.

Sauna usage may very well be keeping life expectancy higher than it should be, given the other risk factors. Research indicates that using a sauna 4-7 times per week confers a 40% reduction in all-cause mortality and even greater reductions in heart related deaths among middle aged Finnish men, which is the cohort most at risk of dying. These numbers, coupled with the numerous protective mechanisms outlined in the last sauna post, lead me to believe that saunas are helping, not hurting Finnish mortality.

Stefan pointed out:

One conundrum is that daily sauna use will sabotage your ballsack precisely because of the heat. Check this old nut-of-a-study: https://ift.tt/2oC5ofi

Sadly, yes. This is a real issue.

What happened in this study?

10 men were recruited to participate. They were in their 30s, generally healthy, and, at baseline, had normal sperm parameters. For 3 months, they each used the sauna at 80-90?C twice a week for 15 minutes per session. Sperm parameters were tested at the start of the sauna use, after 3 months of sauna, and at 3- and 6-months post sauna. They included:

Sex hormones (testosterone, estradiol, FSH, LH, sex hormone binding globulin)

Sperm count (absolute number of sperm)

Sperm motility (ability of sperm to move independently and perform necessary functions)

Sperm histone/protamine ratios (indicative of sperm quality; smokers��� sperm more likely to have dysfunctional ratio, for example)

Sperm mitochondrial function

After three months of sauna, almost every parameter was negatively affected. Sex hormones remained the same, but sperm count and motility were greatly reduced. The proportion of sperm with dysfunctional histone/protamine ratios increased. Sauna increased the number of sperm with poor mitochondrial function. Luckily, everything returned to normal 6 months after sauna use stopped. But still, that’s a big effect.

This seems like a strong mark against using saunas when you’re trying to conceive. The doses were realistic (15 minutes a day, twice a week) and the effects significant. Not only do saunas appear to lower sperm count and motility, they may decrease the genetic fitness and quality of the surviving sperm. This could increase the risk of miscarriage and even have long term effects on the offspring,

If you’re an older guy uninterested in conceiving, this study shouldn’t affect your sauna habits. Sauna doesn’t affect your sex hormones, which have an outsized effect on the quality of your life. It just reduces the viability of your sperm.

If you’re a younger guy interested in having kids, don’t ignore these results. Avoiding saunas for 3-6 months before trying to conceive might be a good idea.

So, in the name of being seasonal and living naturally, what about just getting out in the heat (and not having an air conditioner–but yet cooking a lot) in the summer and being out in the cold in the winter and keeping the house temp low? Is that enough heat/cold exposure to have beneficial effects? (Might be harder to study.) Instead of taking the time to do something extra that takes up natural resources to create, get the exposure through living. Spend half the year hot and half the year cold. (Plus the cold exposure of going to the grocery store in hardly any clothes in the summer, and the heat exposure of going to someone’s house or the local school dressed for cold in the winter.) (Of course this only works in places that have different weather in the seasons.) Isn’t that more along the lines of Grok-ness?

This is ideal, yes. It’s a great point.

There’s actually some evidence that exposing oneself to cold and hot ambient temperatures, rather than maintaining a steady 70º at all times, is good for us.

As I pointed out in an older post, the general trend is that the more people are exposed to predictable, constant ambient temperatures through central heating, the more likely they are to gain weight. In mice, keeping all other variables (diet, activity, etc) the same while switching to a “thermoneutral” ambient temperature (the temperature at which organisms can maintain body temperature without expending any extra energy) triggered inflammation, increased atherosclerosis, ruined blood lipids, and made the mice obese.

Mild cold exposure (just a few degrees’ worth) was enough to activate brown fat (the metabolically active form that kicks in to keep us warm, burning calories in the process) in people. They achieved it by setting the thermostat a bit lower than normal—nothing extreme like ice baths.

I see saunas and cold baths as extreme stressors that address extreme deficiencies. Just like intense workouts can mitigate the effects of sitting around all the time and failing to get the constant low-level movement our physiologies expect, intense heat or cold exposure can mitigate the effects of indoor climate control. But they’re probably not enough. It’s probably better—and certainly more Primal—to also keep the heat down in the house, walk around in the cold in short sleeves, and get comfortable with hot weather.

One thing I’ve been experimenting with is limiting the amount of time I use the AC. I’m trying to just deal with hot days, whether by walking around in as little clothing as possible or creating air flow with open doors and windows. AC has always felt”stale” and “artificial.” I still use it when it’s unavoidable, but I’m beginning to almost enjoy the sensation of low level heat.

That’s it for today, folks. What’s your take on all this? Anyone conceive despite using the sauna? Anyone else trying to vary the ambient temperature in their life? Let me know down below.

Thanks for reading!

Tanskanen J, Anttila T. A Prospective Study of Social Isolation, Loneliness, and Mortality in Finland. Am J Public Health. 2016;106(11):2042-2048.

Laukkanen T, Khan H, Zaccardi F, Laukkanen JA. Association between sauna bathing and fatal cardiovascular and all-cause mortality events. JAMA Intern Med. 2015;175(4):542-8.

Garolla A, Torino M, Sartini B, et al. Seminal and molecular evidence that sauna exposure affects human spermatogenesis. Hum Reprod. 2013;28(4):877-85.

Giles DA, Ramkhelawon B, Donelan EM, et al. Modulation of ambient temperature promotes inflammation and initiates atherosclerosis in wild type C57BL/6 mice. Mol Metab. 2016;5(11):1121-1130.

Chen KY, Brychta RJ, Linderman JD, et al. Brown fat activation mediates cold-induced thermogenesis in adult humans in response to a mild decrease in ambient temperature. J Clin Endocrinol Metab. 2013;98(7):E1218-23.

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