Endocrinology of Reproduction part 1

(This lecture has so much Comic Sans in it. Sooooo much...)

Sexual Differentiation

Firstly, some definitions. There are three levels of sexual differentiation:

1. Genetic sex: XX vs. XY
2. Gonadal sex: ovaries vs. testes
3. Anatomical sex: female genitalia vs. male genitalia

Genetic sex is determined by which sperm meets the egg. Nothing more here, so moving on...

Gonadal sex is determined by the presence (or absence) of the Y chromosome. Being a girl is the default state, but a person can become a guy if they have a Y chromosome. More specifically, the H-Y antigen in the SRY (sex-determining region of Y chromosome) is responsible for the formation of testes. Formation of testes then leads to the secretion of androgens, which then leads to male genitalia.

Anatomical sex is determined by what hormones are present, so in a way gonadal sex determines anatomical sex (as gonads determine the presence or absence of testosterone).

First, I'll talk about the internal genitalia (the tubes and all that). Originally, we have two pairs of ducts: the mesonephric (Wolffian) ducts, and the paramesonephric (Müllerian) ducts. (I'll talk about these a bit more when I get onto studying for ANHB2212.) In the male, Sertoli cells in the testes secrete AMH (Anti-Müllerian Hormone) which causes the Müllerian ducts to degrade, while Leydig cells (also in the testes) maintains the Wolffian ducts. In the female, absence of testosterone causes the Wolffian ducts to degrade, and absence of AMH prevents the degradation of Müllerian ducts.

As for the external genitalia, we all start with a genital tubercle, urethral folds and a urogenital slit. The genital tubercle develops into the penis or clitoris, the urethral folds develop into the labia or scrotum and the urogenital slit develops into the vaginal opening and urethra (in the female, not sure about the male). Testosterone is pretty important here too: testosterone, as well as dihydrotestosterone (which is basically just testosterone after undergoing a reaction catalysed by 5α-reductase) both lead to the development of male external genitalia. Some people have a 5α-reductase deficiency, causing them to have a micropenis or suffer the "penis at 12" syndrome (where they only get a penis when they hit puberty and their testosterone levels peak. Not nice when you'd thought you were a girl for all of your childhood). Some people also have androgen insensitivity syndrome, so even if they are producing these enzymes, they won't get the effects.

Neuroendocrine Control of Reproductive Function

The main thing you need to remember here is that the hypothalamus secretes GnRH (gonadotropin-releasing hormone), which then goes to the anterior pituitary and stimulates secretion of LH (luteinising hormone) and FSH (follicle-stimulating hormone). LH and FSH then go to the gonads to stimulate all the processes that help us become fertile. For the most part, LH stimulates hormone secretion whereas FSH stimulates germ cell development.

First, we'll start off by looking at GnRH, as that has the same effects in both sexes. GnRH has a pulsatile release- that is, it is released in pulses every 2 hours or so, rather than a continuous stream. This pattern does change a bit throughout life- GnRH is high in the fetal and neonatal stages as that's when we get our genitalia, goes down when during childhood, and rises again when we hit puberty. It later drops off past our main reproductive years. Additionally, GnRH release may vary throughout the month with a woman's reproductive cycle.

Reproduction in the Male

Now we'll look at the male, and how sperm are developed. Spermatogenesis takes place in the seminiferous tubules of the testes, which contain spermatogenic cells (will become sperm) and Sertoli cells ("nurse cells" that nourish the spermatogenic cells). Sertoli cells are joined by tight junctions, which are the basis of the "blood-testis barrier" which keeps nasty stuff away from the sperm. It also secretes seminiferous tubular fluid which contains androgen-binding protein as well as some hormones. Sertoli cells are also able to phagocytise damaged sperm.

Back to the growing sperm! Spermatogenic cells originally start on the basement membrane of the seminiferous tubules, and gradually make their way towards the lumen as they mature. As they move, they can cross the tight junctions of the Sertoli cells by breaking those junctions, which then re-seal behind them. As spermatogonia (original sperm cells) mature and divide, they become primary spermatocytes, secondary spermatocytes and finally spermatids. Spermatids are temporarily connected by cytoplasmic "bridges." You see, half the sperm cells will have a Y chromosome, which contains less information than the X chromosome. These "bridges" therefore help proteins and so forth encoded on the X chromosome to make their way into the sperm that only have a Y chromosome.

A developed sperm has a head, body and tail. The tip of the head contains an acrosome, which contains enzymes for digesting the barriers around the ovum. The head also contains the nucleus, which takes up most of the room in the head. The body contains mitochondria, and the tail allows the sperm to swim to its destination.

This is a somewhat abrupt place to end a post, but that's where the lecture ended. The next post will talk more about the hormones, like LH and FSH.