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28 August 2006
Testosterone The Key To Embryo Sex Selection?
by Paul Aitken

When I was a snotty adolescent punk, I got into a debate with my father about, of all things, the wisdom of nature. "Nature isn't wise, Dad, it doesn't have a brain!" My father took a more holistic view and cited the fact that more boys than girls were born following the two world wars - presumably to replenish the decimated male gender - as an example of nature's wisdom.

I hadn't heard that before so I did what any know-it-all adolescent does in such situations: I denied it completely. "Impossible," I snorted. "First of all, how would nature 'know' that a great chunk of the male gender had been killed off? And how would nature 'respond'? Wave a magic wand and presto! More male babies?" A little bit of knowledge is a dangerous thing and I had recently learned about X chromosomes and Y chromosomes and the fact that any one sperm had one or the other and therefore the gender of any baby, fetus or blastocyst was a strictly 50-50 proposition. I even remember my biology teacher talking about the irony of Henry VIII executing his wives because they couldn't give him male children when in fact the gender of his progeny was determined entirely by his sperm!

I can't remember how the debate ended and I can't say my opinion has changed. I still don't believe nature possesses "wisdom." But nature has certainly turned out to be far more complex and mysterious than I had imagined in my adolescent certitude. For one thing I've since learned that the ratio of male to females born is NOT a 50-50 proposition at all. There are in fact around 105 human males born to every 100 females. This is not a statistical anomaly. It cuts across all ethnic groups. But it's not a global constant either. Amongst Africans and Amerindians the figure is 102:100, suggesting a genetic mechanism is at work. It's possible, even probable, that this is an evolutionary adaptation to counter the gender imbalance that arises in late adolescence. In every culture young men are prone to dying young and stupidly. In primitive tribes the cull rate is over 25 percent. I also learned that my father was correct. During and after both world wars there was a spike in the birth of male babies. This is an astounding fact and one I still have trouble digesting. How did nature "know" there was a war? How was she able to respond in the way she did? What exactly determines the gender of a baby?

The answer has been the same since we discovered chromosomes. XX = girl. XY = boy. End of story. Gender is genetic. Hormones may play a role in how gender manifests itself - bathe an XX fetus in the wrong hormones at a critical stage in development and she'll be a chick with a dick - but genetically she'll still be a girl. The female ovum only carries an X chromosome. That means gender is determined by the sperm. Given that there are an equal number of X and Y sperm produced, one would expect there to be an equal number of male and female births. This obviously isn't the case, so somewhere between the balls and the baby; something is giving the Y gene a leg up. But what?

Let's start with the sperm themselves. Could Y sperm have a natural advantage? Could they be, ahem, superior to X sperm? Well... yes, as a matter of fact. It comes down to basic physics. The Y gene is considerably smaller and lighter than the X gene. Given that speed is a product of force and mass; all things being equal Y should be faster and this is a race after all. The "Y is lighter" theory has been suggested to account for the fact that more boys than girls are conceived in the early stages of ovulation when the sperm must pass through a thick mucus plug at the entrance to the uterus. Once ovulation begins, the mucus plug develops watery channels and progress is much more a matter of chance, but before then it's a long hard slog and small advantages come into play. But is the weight advantage enough to account for the 105:102 ratio?

Early ovulation conception is fairly rare and while the difference in mass between Y and X is real, it is also negligible. The nucleus is a tiny fraction of the weight of the sperm and the weight of one chromosome is a tiny fraction of that. And what about that post war spike and other statistical quirks? Not only are more boys conceived in the early stages of ovulation, they're also favored in late ovulation. The length of the follicular period also appears to be a factor as does birth order (more boys born first) birth interval (short intervals favor boys) the age of the mother (older women give birth to more girls) and as we've already seen, ethnicity. Chromosomal mass differential may be a factor in the sex ratio, but it's not the only one and probably not the main one.

But one factor seems dominant and in fact may be able to account for most, if not all, the aforementioned statistical curiosities: hormones. In the period before and after conception, the sperm and the ovum are bathed in a number of different hormones the proportions of which vary according to the stage of ovulation, the status of fertilization and the state of mind of the mother. The latter may seem a stretch until one remembers that many personality traits are hormonally driven (think PMS). Dominance, driven by serum testosterone, (the amount of testosterone present in the blood - yes, women produce testosterone too!) seems to be an important determinant in the sex ratio. Mothers who score in the top quintile on dominance have on average five times more boys than those who score in the bottom quintile. This surprising statistic underpins what's become known as the Maternal-Dominance Hypothesis (MDH). Big-time MDH fan, Dr. Valerie Grant, contends that the tendency for dominant women to have male babies is an evolutionary adaptation. Not only are dominant women better suited to raising male children; high status women tend to raise high status sons. And because male status is attractive to women (how else do you explain Billy Joel and Christie Brinkley), these sons are more likely to be genetically successful than daughters, whose ability to reproduce is ultimately limited by the relatively small number of eggs they were born with.

While the molecular mechanism by which higher serum testosterone favors an XY conception is still unknown, there is speculation that testosterone affects the manner in which sperm passes through the clot of cells that surround the ovum (the zona pellucida). As I explained in "Mr. Sperm Goes to War", passage into the zona pellucida (ZP) is determined by a matching of surface proteins between the acrosome (head) of the sperm and the outer layer of the ZP. Recent studies have shown that while gene transcription is rare during sperm differentiation, some Y genes are expressed in the formation of the acrosome. This suggests a mechanism by which the ovum can recognize, and possibly favor, a Y sperm.

The high serum testosterone theory goes a long way to explaining why more first-borns are male. Young women have higher levels of serum testosterone and these levels are most pronounced in the first few months of a sexual relationship when sex is frequent and conception likely to occur. It also explains the preponderance of male babies born during and shortly after the two major wars. Serum testosterone levels in women are not constant. Like other hormones, testosterone is subject to flux depending on a woman's psychological state. Women working in traditionally masculine occupations such as law have been shown to have higher levels of serum testosterone. And no, this isn't just because high testosterone women are attracted to such occupations. Studies have shown that the type of work women do changes their testosterone level. So it stands to reason that when women were responsible for holding up the homefront during the war (they worked in factories, played professional baseball), they could very well have experienced elevated testosterone levels.

If the testosterone theory is correct it has enormous implications. For one, it could provide a means by which couples could influence, or even choose, the gender of their children. This may be good or bad depending on your ethical point of view, but there's no denying the value to parents desperate for one sex or the other. In a double irony it turns out that Henry VIII's choice of wives may have had some bearing on his inability to sire a male heir after all. If only Anne Boleyn had worn a testosterone patch history might have been very different.

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