Life is Sex (Part I)

How did I become male/female?

Although the sex of a person doesn’t affect their ability to survive, without males and females the human race wouldn’t exist. You might be interested to know that no matter whether it’s male or female every human embryo begins with the same pre-sexual set-up. The development of this tissue into what will become a fertile male is directed by six important molecules. If any one of them is missing the human embryo either becomes female or an infertile male. In other words, each of these six molecules must be present to have a fertile male and with him the existence of the human race hangs in the balance.
In the beginning when the sperm of your father met the egg of your mother they fused to become you: a one celled zygote in your mother’s womb. You had twenty-three pairs of chromosomes, one of each coming from your father and mother. One pair, X and Y, were the sex-chromosomes, which decided which sex you would be. A female usually has two X chromosomes. So,whether you’re male or female, your mother provided you with one X. A male usually has an X and a Y. So, if you’re a female your father gave you an X and if you’re a male he gave you a Y.

Soon after you came into being as a zygote your one cell started to divide until you became an embryo. Like all human embryos your pre-sexual tissues were the same. You had undeveloped gonads that would become ovaries or testes. You had undeveloped female internal genitalia which if turned on would become the uterus and upper vagina. You also had undeveloped male internal genitalia which if turned on would become the epididymis, seminal vesicles and vas deferens (tissues that take care of the sperm). And you had undeveloped external genitalia which would become the lower vagina and vulva or the penis, prostate and scrotum. So, at this point, you were ready to become either male or female. So what’s next? Let’s see how these six molecules do their jobs.
The first and most important molecule, the one that starts the embryo down the male track rather than the female one, comes from the Y chromosome. Without this molecule the embryo will automatically become female. That’s why a person who is XX becomes female and a person who is XY becomes male. This molecule is called the Testes-Determining Factor. If you’re a male this molecule went to your undeveloped gonads and told them to become testes when you were about seven weeks old. If you’re a female, because you didn’t have this molecule, your undeveloped gonads automatically became ovaries.

The second molecule that’s necessary for having a fertile male is testosterone. Once the undeveloped gonads become testes they start to make this male sex hormone. They do this by taking cholesterol and applying six different enzymes to it to change it into testosterone. None of these six enzymes comes from the Y chromosome. They come from the twenty-two other pairs. So, you can see that although the Y chromosome is needed to have a male, it’s not the only one.

The third important molecule is called the androgen receptor. It’s what testosterone attaches to so it can have an effect. Testosterone attaches to the androgen receptors on the cells that make up the undeveloped male genitalia and tells them to become the epididymis, seminal vesicles and the vas deferens. Without testosterone or androgen receptors these cells automatically die. Now you can see why they’re both important for getting a fertile male. The information for making the androgen receptor is on the X chromosome. So, although the Y chromosome starts the embryo down the male track he still needs the X chromosome for him to turn out right.

Whether there’s testosterone and androgen receptors, or not, the undeveloped female internal genitalia (Mullerian ducts) automatically become the uterus and upper vagina unless prevented from doing so. If this were to happen in the male it would make him infertile because the two sets of internal genitalia would become entangled. That’s where the fourth and fifth molecules to make a fertile male come in. The testes not only make testosterone but also another molecule called Anti-Mullerian Hormone. It attaches to specific receptors on the cells that make up the undeveloped female genitalia and tells them to die. The information to make Anti-Mullerian Hormone is on the 19th chromosome and for its receptor it’s on the 12th chromosome. So, you can see why all of the genetic information is needed to get a fertile male, not just X and Y.  

Without testosterone and androgen receptors the undeveloped external genitalia automatically become the lower vagina and vulva. But to get proper male external genitalia, which allows the male to perform sexually, involves another twist. It turns out that these particular androgen receptors don’t respond well enough to testosterone to do the job right. To do that, they need to be stimulated by dihydrotestosterone otherwise the penis, prostate and scrotum will be deformed. So, the sixth molecule needed to get a fertile male is the enzyme that changes testosterone into dihydrotestosterone. The information for it is on the 2nd chromosome.

Without Testes Determining Factor or any of the six enzymes needed to change cholesterol into testosterone or the androgen receptor, the human embryo automatically becomes female. And without Anti-Mullerian Hormone or its receptor or the enzyme that changes testosterone into dihydrotestosterone you get an infertile male. All six of these molecules have to be present to have a fertile male and with him the human race.

But sometimes life can surprise us. Take for example the XY female. An XY female is a person who looks like a perfectly normal female but instead of being XX is XY instead. When they’re born they look female and they mature like a normal female with normal breast development. It’s when they don’t menstruate that they seek medical attention. It’s then that they find out that they have a short vagina leading to nowhere, no uterus, and inside they have testes instead of ovaries. The problem with the XY female is that their androgen receptors don’t work. In other words, even though they have lots of testosterone it has no effect on them. 

Here’s how it plays out.                                                                               

Since the XY female has a Y chromosome it has the Testes Determining Factor which goes to the undeveloped gonads and tells them to become testes. The testes make testosterone but it can’t have its affect on the undeveloped male internal genitalia because her androgen receptors aren’t working, so they die. However, her testes also send out Anti-Mullerian Hormone which attaches to its specific receptors on the undeveloped female internal genitalia and they die too. So that’s why the XY female doesn’t have male or female internal genitalia. And since her testosterone can’t have an effect because her androgen receptors don’t work, her undeveloped external genitalia become female. So, that’s why when she matures, she looks like a normal woman.

If you’re a thinking person you may be wondering how the XY female can have normal female breasts if she has testes that make testosterone rather than ovaries that make estrogen. It turns out that the development of the female breast is dependent, not on the absolute amounts but the ratio between estrogen and testosterone (E/T). A mature male normally has a very high level of testosterone and a very low level of estrogen (derived from testosterone), so his E/T ratio is very low and that’s why his breasts don’t develop. A mature woman normally has a very high level of estrogen and a very low level of testosterone so her E/T ratio is very high and that’s why her breasts develop. The XY female is like the mature male in that she has a very high level of testosterone and a very low level of estrogen. But in her case, because her androgen receptors don’t work it’s like she has no testosterone at all. This means that her E/T ratio is E/0 which approaches infinity and is why her breasts develop. It’s been said that some XY females are the most beautiful and feminine women in the world because the male hormone within them has absolutely no effect.

3 Questions for Mr Darwin

1. How did life figure out that it mostly needed to split up the genetic material and put them in male and female gametes and then bring them together to bring about new life?

2. How did life anticipate the need for each of the parts required for human reproduction, where did the information come from to make the undeveloped sexual tissues and in what order did they come into being?

3. Where did the information come from for the six different molecules needed to make a fertile male rather than an infertile or female one and absent one or more of them, how did sexual reproduction take place in the life forms leading up to us?

 


Also see Dr. Glicksman's Series on

"Beyond Irreducible Complexity"

"Exercise Your Wonder"


Howard Glicksman M. D. graduated from the University of Toronto in 1978. He practiced primary care medicine for almost 25 yrs in Oakville, Ontario and Spring Hill, Florida. He now practices palliative medicine for a Hospice organization in his community. He has a special interest in how the ethos of our culture has been influenced by modern science’s understanding and promotion of what it means to be a human being.

Comments and questions are welcome.

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