#embryological

[markscherz]

now accepting guesses as to what this embryo becomes when it matures

[jcrmhscasereports]

COMPLETE PENOSCROTAL TRANSPOSITION WITH MULTIPLE CONGENITAL MALFORMATIONS by Jafari B. Lutavi in Journal of Clinical Case Reports Medical Images and Health Sciences  

SUMMARY

Penoscrotal transposition (PST) is an extremely rare congenital anomaly of the external genitalia, characterized by malposition of the penis in relation to the scrotum. PST can be either complete or incomplete according to the positional exchanges between the penis and scrotum and both forms of PST are generally linked with hypospadias. Incomplete transposition is the common form of this entity and the penis lies in the middle of the scrotum, but complete transposition, the scrotum almost entirely covers the penis, which emerges from the perineum. Both forms are most often associated with a wide variety of other anomalies. We describe a case of a newborn with complete PST, with other associated malformations.

BACKGROUND

Penoscrotal transposition (PST) is a rare anomaly of the external genitalia, characterized by malposition of the penis in relation to the scrotum1,2,3. PST can be defined as either complete or incomplete according to the positional exchanges between the penis and scrotum and both forms of PST are generally linked with hypospadias. Incomplete transposition is the common form of this entity and the penis lies in the middle of the scrotum, but in complete transposition, the scrotum almost entirely covers the penis, which emerges from the perineum1. PST was first reported by Appleby in 1923. Patients with PST often have accompanying urological abnormalities, such as chordee, hypospadias, and vesicoureteric reflux4.

The etiology and embryological sequence abnormalities that occur in PST is still unclear. The genital tubercle and the labioscrotal swellings are the embryological origins of the penis and scrotum, respectively. During normal embryonic development, in the 9th–11th week, the scrotal swellings migrate infero-medially and fuse in the midline caudal to the genital tubercle that forms the penis by the 12th week of gestation. This is usually achieved under the influence of androgens and poor response or absence of androgens results in abnormal migration  of the scrotal swellings3. Somoza et al suggested that an abnormal positioning of the genital tubercle at the 6th gestation week (GA) concerning the scrotal swellings or a defective gubernaculum leads to PST2.

Complete penoscrotal transposition (CPST) is frequently characterized by major and often life-threatening anomalies involving the urogenital, cardiovascular, gastrointestinal, and skeletal systems2. Common genital anomalies include hypospadias and chordee, and 100% of cases have a renal defect.

CASE PRESENTATION

A gravida 5, para 1, living 1 with 3 abortions woman aged 27 years was referred from Mwananyamara Referral Regional Hospital and admitted to Obstetrics and Gynecology department at Muhimbili National Hospital- Mloganzila. She has a referral diagnosis of antepartum hemorrhage and severe oligohydramnious at GA of 30 weeks 2 days. She had three previous pregnancy loses: 1st and 2nd loses both at 12 weeks GA with 6 months between the loses; her 3rd loss was 2 years after she had a term healthy baby by normal delivery.

She had no histories of phenotypic genetic abnormalities in their families, illicit drug use, cigarette or alcohol consumption, no chemical, radiation exposure, or any chronic illness. She is married, and is a university graduate, working as a transportation officer. She attended antenatal clinic (ANC) five times and all her laboratory work-up such as blood count indices, blood grouping, urinalysis, stool examination, and microscopy, and fasting blood sugar were normal. She was HIV negative and blood film for malaria parasites came back negative. Record of the ultrasound scan taken at 6th -week gestation indicates early multiple pregnancy (two gestational sacs seen) and the next scan performed at 27th weeks GA show a normal single fetus with no anomaly. She was given iron and folic acid supplements, received Tetanus Toxoid vaccine twice, sulfadoxine-pyrimethamine (SP) tables twice as part of intermittent preventive therapy for malaria and she was dewormed using Mebendazole. With her history of pregnancy loss and complaints of abdominal cramps, she had been kept on bed rest at home from 16th week of gestation as recommended by her obstetrician at Mwananyamala Hospital.

After she was brought to our hospital she had active vagina bleeding. A bed side ultrasound revealed placenta previa grade 3 and she was planned for emergency hysterotomy. She delivered a male baby, 1750 gm, who did not initiate spontaneous breathing after birth. The baby was initially resuscitated with a bag and mask before intubation at age 5 minutes. He was assigned an Apgar score of 3, 1, 4 at 1st, 5th and 10th minute respectively. On examination, baby had severe pallor, occipital-frontal circumference – 29cm, communicating anterior and posterior fontanelle, low set ears, short neck, wide-spaced nipples, undescended testes (empty scrotum), inverted genitals (CPST) with hypospadias (Figure 1), rectal atresia, prominent heel, and bilateral talipes equinovarus.

https://jmedcasereportsimages.org/wp-content/uploads/2022/10/fig-1-2.jpg

Figure 1: (a) shows a horizontal view of complete penoscrotal transposition and (b) shows an oblique view of complete penoscrotal transposition.

DISCUSSION

Penoscrotal transposition (PST) is a congenital urogenital anomaly described first in 1923 by Appleby. The embryological sequence responsible for this malformation remains unclear; however, it has been suggested that an abnormal positioning of the genital tubercle in relation to the scrotal swellings during the critical fourth to the fifth week of gestation could affect the migration of the scrotal swellings2. In this case report, there is a complete exchange of position with the scrotum located superior to the penis, which is inferior to scrotum. (Figures 1(a) and 1(b)). Also, there presents a spiral and hypoplastic penis crooked toward the anal position. Ayamba et al reported the same findings whereby noticed complete transposition of the external genitalia with cryptorchidism, hypoplastic penis from the perineum just above the blind anal position, and caudal to the scrotum3. Somoza et al also noted at birth a newborn has a complete transposition of the external genitalia, a 3.5-cm-long, hypospadic, and hypoplasic penis arose from the perineum, just above the anus and beneath a normal scrotum1–3,5.

CPST is often characterized by major associated malformations. Our baby had also other multiple physical abnormalities such as short neck, low set ears and talipes equinovarus. Unfortunately, due to our limited resources, we could not complete imaging of internal organs. Previous reports of CPST have also noted presence of other malformation with 100% occurrence of renal anomalies. For example, Parida et al had noted major renal anomalies in the form of agenesis, horseshoe kidney, ectopic and dysplastic kidney, obstructive uropathy, and hydronephrosis. Other systemic abnormalities are mental retardation, anorectal malformations, central nervous system, skeletal and cardiological defects5.  In our case, we did not perform imaging to detect renal anomalies, but literature suggests most likely there were there. The detection of CPST should warrant careful clinical evaluation to rule out other anomalies.

Although some reported a family history and genetic basis for the incidence of PST6, we did not find any evidence of positive family history of phenotypic abnormalities. When associated with severe hypospadias, penoscrotal transposition necessitates a staged surgical repair for physiological and psychological reasons.

Our newborn required advanced resuscitation at birth, likely due to hypoxia in utero as a result of significant blood loss (placenta previa grade 3). This is supported by the findings that baby was very pale at birth. However, we cannot rule out the possibility of other anomalies such as fatal cardiac anomalies which are incompatible with life1,5.

OUTCOME

The newborn was transferred to the neonatal intensive care unit for further treatment and passed on after 4 hours. No any radiological or laboratory investigation were completed within this time.

LEARNING POINTS/TAKE HOME MESSAGES

Strengthening of antenatal care services in a primary health facility is a key for positive outcome of pregnancy. This is by early detection of abnormal development of fetus in utero by early ultrasound

Referring hospitals in low-income settings should be strengthened with well knowledgeable personnel (radiographers) and modern equipment. As we have notice in this case even a placenta praevia was detected after being received in a tertiary hospital despite the woman being scanned in late 2nd

There is a need of strengthening neonatal ICU by ensuring bedside radiological equipment’s is available also other ICU equipment’s are enough. As we have seen no any radiological investigation done to the baby due to the fact that the baby was in critical condition but based on critical care knowledge and experience this could possible by bedside equipment.

Learning culture must be strengthened in our institute; if we had good learning culture radiological investigations would have been done to the dead baby for learning purpose to detect if there is any other internal congenital anomaly and other cause of death to this newborn

PATIENT’S PERSPECTIVE

Am so thankful for the services I receive from all hospitals and I declare to have no any experience of having an abnormal baby in my family and even my husband’s family. This is my first time to give birth a newborn with congenital malformation and i wondered the way it was not even discovered early during the antenatal period. Also, I promise to attend the clinic early for the next pregnancy and follow all instructions that i will be given by health care providers for the sake of the good health of herself and next baby.  Am so happy about this publication because it will help other doctors to identify the condition and treat it accordingly also for those who are in learning schools will learn more about this condition.

Competing interests: None.

Patient consent: Obtained

For more information: https://jmedcasereportsimages.org/about-us/

For more submission : https://jmedcasereportsimages.org/

[bloodbruise]

attending!james bringing med student!reg coffee each time he's been at the books for hours. he just wordlessly puts it down, slips his arms around regulus' waist and kisses the tension out of his jaw. hums along while regulus rants about germ layers, embryology, the whole unintuitive mess of it. has to stifle his smile in the back of reg's neck because, yeah he's been there too.

[secularprolifeconspectus]

My friend is 9 weeks pregnant! Her embryo is 7 weeks gestation. We call them Frijole and in this video they roll over, suck their thumb and wiggle their toes. You can also see their heart thumping!

[nemfrog]

"Development of body form in pig embryo." Comparative embryology of the vertebrates. 1953.

Internet Archive

[o-craven-canto]

Embryophylogeny

(original picture here)

A map showing the derivation of various structures and tissues of the human body from the parts of the early embryo.

Human figure partly traced from this Wiki Commons image (public domain). Main source is TW Sadler, Langman's medical embryology (12th ed.), 2012.

[tpup]

That’s actually not a pussy seam. It’s a penis line. That’s ok! It doesn’t make you not a woman to have a penis! But it also is not a pussy line bc it’s a penis. 😊

anon who is feeling smug about their transphobia is wrong about biology. nobody is shocked or impressed by them, + I continue to tonguefuck pussy seam

[nochd]

This came across my dash via the #lgbt tag yesterday. I don't want to engage with the OP because that would get me into fights on radfem tumblr and I don't have the energy for that. But the post itself I think is worth answering, just because it's so neatly and exactly wrong.

(Not that my answer is going to spread very far, because I have 37 non-bot followers, of whom I think roughly 35.5 are just here for the nude photos. But anyway.)

Even if I agree just for argument's sake that the existence of intersex people proves that some people can have "nonbinary" sexes, or "third" sexes, and that "sex is a spectrum," how does that have any relevance to people who are not intersex? Like okay, let's "agree" for the moment that intersex people are something other than male or female. How does that make YOU, as a person who is not intersex, something other than male or female? Saying that intersex people's existence somehow makes sex "complicated" for you specifically is like saying that the issue of whether or not you can hear is "complicated" because some other people who are not you suffer from hearing loss or deafness. Like sorry but for 99% of the human population it is not "more complicated" than born with perfectly normal male genitalia = male and born with perfectly normal female genitalia = female, and chances are you fall into that 99%. Sex is not a social construct or a nebulous enigma of a concept. It is not debatable and made up in the manner that gender is. You cannot philosophize about whether there are two sexes any more than you can philosophize about whether humans have two kidneys. Someone having a missing or malformed kidney or accessory kidneys does not change the fact that humans as a species have two kidneys. Humans are gonochoric just like nearly all other animal species on Earth.

Let's start with the arithmetic. If 99% people are of binary sex, that leaves 1% of people who aren't. There are approximately 8 billion humans on Earth. 1% of 8 billion is 80 million -- about sixteen times the population of my entire country. Even just the number of intersex Americans is something like two-thirds the population of my country. This is not a negligible number of people.

There's a deeper error here, one that goes to the root not just of this misunderstanding but of many. Biology is always complicated, at every scale and at every level of explanation. It's messy, it's fuzzy, and it's always bottom-up, never top-down. Everything biological is the way it is because it grew that way. Biology never does the same thing twice.

Why does it seem like it does? Because, of all the ways you can arrange the parts of a living body, only an astonishingly tiny fraction of them actually make a living body. Any genetic mutation that nudges an organism outside of that fraction dies out and doesn't get passed on. Embryonic development is a gruelling tight-rope walk over a vast pit of non-existence.

Now for most of the body's systems, evolution has only had to produce one arrangement that works and survives. There's not an alternative plumbing plan where the oesophagus goes to the lungs and the trachea to the stomach. But for the reproductive system, evolution has to allow for two arrangements that work and survive, and it has to grow them both from the same starter kit.

What it does, therefore, is grow a body plan that works with a continuum of possible arrangements that includes both of those two. Various other points on the continuum may or may not be capable of producing viable gametes, but they're all survivable.

What biology doesn't do -- what biology never ever does -- is run new products on a conveyor belt stamping them into shape with cookie-cutters. The only things made that way are artificial constructs.

[bat-snake]

In all seriousness though, I love that how, even though Leola has one horn, it has two branches, which just makes me Think Things about elf embryology (if she even developed from an embryo to begin with???)

Like...they probably START with a single horn that's supposed to split and move to the top of the skull as cell division goes along, but that never happened with Leola. Yet the genes for two horns kept going anyway...so we get the single horn with a small branch coming off it, in the middle of her forehead.

Single horns could also be regarded as one of the first signs that a baby might be neurodivergent. (Obviously not EVERY "unique and quirky" elf has had a single horn, but all single horned elves have been "unique and quirky")

[cheerfullycatholic]

[biologist4ever]

𝐈𝐧𝐭𝐚𝐜𝐲𝐭𝐨𝐩𝐥𝐚𝐬𝐦𝐢𝐜 𝐒𝐩𝐞𝐫𝐦 𝐈𝐧𝐣𝐞𝐜𝐭𝐢𝐨𝐧

 𝐓𝐡𝐞 d𝐫𝐞𝐚𝐦 𝐨𝐟 s𝐭𝐚𝐫𝐭𝐢𝐧𝐠 𝐚 f𝐚𝐦𝐢𝐥𝐲 𝐰𝐢𝐭𝐡 d𝐢𝐫𝐞𝐜𝐭 f𝐞𝐫𝐭𝐢𝐥𝐢𝐳𝐚𝐭𝐢𝐨𝐧

[euoniaisanelusion]

As great as Cantiques´ "Embriology" (AO3) is and how many tears I shed over chap 20, it will forever be so legendary to me that the entire story is nothing but buildup for what is essentially a LITERAL "Chris is that a weed??!"moment" and its fallout :´)

[rose-maidenn]

Developmental biology , Scott F. Gilbert

[pseudomonaslisa]

the way people talk about the reproductive system vs other body systems is so weird. "each sperm furiously tries to be the first to get into the egg" what the fuck are you talking about. it's dna with a flagella. nobody says "the urinary bladder desperately contracts to get all of the pee out 😖😩"

[nemfrog]

Chicken embryo at 20 hours. Comparative embryology of the vertebrates. 1953.

Internet Archive

[o-craven-canto]

The processes that can turn an aggregate of cells into a complex organism. ADH: cell adhesion. APO: apoptosis, or selective cell death. ASM: asymmetrical morphogenesis. DAD: differential cell adhesion, sorting cells by type. ECM: secretion of extracellular material. LAT: lateral inhibition, a switch that can turn a cell into two different states. MIT: mitogenesis, or localized cell division. MOR: diffusion of a morphogenic signal. OSC: timed osclllation between different states. POL: polarization, or differential properties at different ends of a cell. TUR: Turing reaction-diffusion pattern. (pic: Newman & Bhat)

It's all well and good to say that DNA contains the instructions to produce an organism, but all DNA can do is induce the secretion of chemicals. There are no printed instructions or little foremen supervising the growth of an embryo. So how does secreting chemicals in a clump of identical cells end up producing something as complex as an animal?

Here's some tricks.

Differential adhesion. The cells of all animals have surface proteins called cadherins that bind each other into solid tissues. If all cells were uniformly covered in cadherins, they would form homogeneous spherical lumps; but if some cells are covered more or less sparsely than the others, then they will spontaneously sort by cadherin density, forming clumps and layers much like the spontaneous sorting of water and oil. If some surfaces are not adhesive at all, those will find themselves surrounding cavities. (pic: Gilbert & Barresi)

Lateral inhibition. The Notch protein forms a trans-membrane complex; when the external portion receives a signal from the environment, the internal portion breaks off and enters the cell nucleus to activate the expression of otherwise repressed genes. Thus, the Notch system works as a switch between two different states of a cell depending on whether or not it receives a particular signal. This is called "lateral inhibition" because it makes neighbor cells, such as neurons and glia in the brain, develop into complementary forms repressing each other's unnecessary genes. (pic: Audrey Effenberger, Wiki)

Cell polarization. "Wnt" is the name of a family of secreted signal proteins that have a multitude of functions. Among this is establishing cell polarity: through a cascade of signals, it can cause the cell's cytoskeleton -- its internal scaffolding -- to rearrange itself into an asymmetrical shape (... I think. This part of the process isn't fully clear to me), which leads to further differentiation. If the polarity involves different types or densities of adhesion proteins, then differential adhesion will sort polarized cells into distinct layers or hollow sacs and tubes -- hence, organs and body cavities. Cell polarization also leads to the establishment of the head-tail and back-belly body axes. (pic: Gilbert & Barresi)

Morphogenic gradients. When a cell or group of cells start secreting a diffusing chemical, this will naturally form a gradient with its concentration fading away with distance. This can direct differential development of cells over the organism body. Even if the chemical gradient is smooth, the morphological one doesn't need to be: cells can have different thresholds that will cause them to take one or another form. So there will be different discrete types of cells, each developing at a fixed range of distances from the source of the gradient. For example, in vertebrates, the protein Shh in the notochord induces the formation of motor neurons in the ventral side of the neural tube, which is closest. (pic: Gilbert & Barresi)

Asymmetrical morphogenesis. But then how do we end up with asymmetrical morphogenesis, for example our heart growing more on the left than on the right side? Morphogens don't have to spread only by themselves: in vertebrates, the morphogenic protein Nodal is systematically pushed to the left by beating cilia. Malformations in cilia can result into situs inversus, the development of organs in a position that mirrors the usual one. In addition (see "reaction-diffusion" below), Nodal induces the secretion of the protein Lefty2 which in turn inhibits Nodal and spreads faster, resulting into a side of the body where Nodal cannot accumulate. (pic: Green & Sharpe)

Chemical oscillation. If gene-activating factors inhibit their own synthesis, then they will come and go in regular waves, growing when they are few and decaying when they are many. This gives cells their own internal clock, which for example allows a cell to replicate at regular intervals. In multicellular organisms, the oscillation occurs in space as well as in time, as growth signals are released in waves. So they determine the formation of regular segments: for example, our vertebrae. (pic: Müller et al.)

Extracellular matrix secretion. While cells in epithelial tissues (like the outer layers of skin, or the lining of body cavities) stick closely to each other, those in connective tissues (like the inner pulp of skin, cartilage, or fat) are sunken in a matrix of various composition, but which usually contains elastic fibers of collagen. When a cell develops into a fibroblast, it starts secreting around itself the component of extracellular matrix with various mechanical properties, affecting the shape and structure of the body (especially when the cell is polarized). Even bone is simply a connective tissue whose matrix in rich in calcium phosphate mineral.

Turing patterns (reaction-diffusion). A chemical produced by a cell activates both itself and its own inhibitor. Activation is powerful but short-ranged; inhibition is weaker but spreads farther. Once a cell has produced the chemical past a critical threshold, its keeps reinforcing its own production, but also inhibits its neighbor from doing the same. At a greater distance, however, another cell or group of cells could also start the synthesis on their own. Depending on the range and power of activation and inhibition, this produces all sorts of patterns of activation: spots, stripes, waves, grids, rings. (pic: Green & Sharpe; Metz &al)

Apoptosis. Cells that receive a certain signal die, and their matter is recycled. If the signal of death is distributed according to Turing patterns, then living tissue can be cut and molded in very precise ways. For example, cells in the developing limb-bud of a vertebrate die in waves leaving behind parallel cylinders: the beginning of fingers.

Multiple mechanisms coming together to make vertebrate limbs: a morphogenic gradient distinguishes base and tip of a forming limb; reaction-diffusion creates a Turing pattern (diverging waves) that determines where finger bones will develop; and finally apoptosis cuts away the intermediate tissue. (pic: Green & Sharpe)

SOURCES

Gilbert & Barresi (2016), Developmental Biology Green & Sharpe (2015), Positional information and reaction-diffusion: two big ideas in developmental biology combine Newman & Bhat (2009), Dynamical patterning modules: a "pattern language" for development and evolution of multicellular form