Thursday, February 6, 2014

Sex differentiation in utero

Week 9- Reproductive organs, continued development of the digestive system- intestines, also buds for teeth form

The major things I remembered about sexual differentiation in the fetus, from when I took development biology in grad school, are there are two pairs of tubes, the Müllerian and Wolffian duct, in all developing babies. For girls, one develops into the internal sex organs and the other recedes and for boys the opposite. Turns out that is a pretty good estimate of what happens. But let’s look a little closer. The two duct pairs are part of urogenital development in the fetus and both extend passed the mesonephros (the primitive kidney) towards the caudal (tail) end of the organism, at the cloaca (define). The fetus remains gender neutral until about the 7 to 8 week, but one major thing has been in effect since way back when fertilization occurred. In terms of sex chromosomes, there are two an X and Y chromosome, each parent contributes one to the zygote to get a set. The mother can only contribute an X chromosome, since women are XX, but daddy can contribute either the X (this gives a daughter) or the Y (this gives a son). Ultimately it made sense for researchers to hone in on gene products from the Y chromosome as dictators of the male phenotype in developing organisms and the SRY gene was found. The SRY gene along with some others induce differentiation of cells located in the up-to-this-point gender neutral gonads to pick a side and become male sex organ lineage. The gonads, as depicted in the image, are a pair of undifferentiated sex organs located alongside the mesonephros and are made up of mesodermal germ cells, supporting cells, and steroidogenic cells.  Each of the sex organs, male or female, have both structural elements and hormone-producing elements. The steroidogenic cells will produce the gender-specific hormones when directed to do so. A major hormone that heavily contributes to gender assignment, along with the Y chromosome SRY gene, is the Anti- Müllerian Hormone. As I mentioned in my brief recollection of what goes on in the fetus for sex assignment to occur one of the aforementioned ducts will become the sex organs and the other duct will degrade. The SRY gene product, the Testes Determining Factor, and other genes along for the undifferentiated gonads to take on male characteristics, the supporting cells become Sertoli cells and the steriodogenic cells become the Leydig Cells, these start to make testosterone by week 8. The germ cells in the gonads will become spermatogonia. So now we have cells that will produce testosterone, Leydig cells, to allow for sperm production and the cells that will support sperm production, the Sertoli cells. The Sertoli cells are production site for the anti- Müllerian hormone, which will allow for the degradation of the female-designed pair of ducts, at the 8 week mark. The Wolffian duct will develop into the epididymis, vas deferens, and the seminal vesicles. In the absence of this testis-determination factor, the ovaries will begin to develop in the gonad region around 12 weeks. In the case of ovaries, the supporting cells will differentiate to Theca cells and the steroidogenic cells will become granulosa cells. I’m not sure how much this nomenclature of calling one cell type supporting and the other steroidogenic holds up in the case of a female since these cells but support the developing eggs, oocytes, and both produce hormones. The granulosa cells directly surround the oocyte and produce the various estrogen hormones, while the theca cells are present in the outer layer and make androgens (which the granulosa cells use to make estrogens). The Müllerian duct will become the uterus, fallopian tubes, and the upper vagina. In terms of external genitalia by week 7 the undifferentiated genital tubercle, urogenital groove & sinus, and labioscrotal folds will become the clitoris, urethra, lower vagina, and labia in the absence of testosterone by week 7. For developing boys between weeks 8 and 12 the genital tubercle will become larger forming the penis, while the urogenital groove and sinus will merge to give rise to the urethra & scrotum.
Gender determination can be done a variation of ways at different points in the pregnancy and for different reasons. There is of course the curiosity factor but in some cases learning the gender is done for diagnostic purposes. An amniocentesis or a chorionic villi sampling can be done as early as 15 weeks.   A blood test at or after 7 weeks or confirmation can be done via ultrasonography between 18 and 26 weeks. Generally the first three options are done for diagnostic purposes.
At this point we have discussed in some detail the kidney and the ureters as well as the sex organs including the urethra, the only thing missing from this discussion of the urogenital system is the bladder. And of course since I broke the two up it’s a little tricky throwing the bladder back in, but it comes from the urogenital sinus (which itself comes from the cloaca). The cloaca is the most caudal part of the hindgut and it splits into different regions forming both the bladder and urethra (the urethra is slightly different depending on whether the baby is a girl or a boy) and the rectum and anal canal. The bladder begins development around the 12 week point.

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