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X Marks the Spot for Male Fertility

Infertile? Blame Mom

X and Y: From Then to Now continued...

Since that time, however, as the human race worked its way up the evolutionary ranks, it seems that the genes that control spermatogenesis -- the creation of sperm -- have become so essential to the species that they've been copied over and over again and shuffled from the garden-variety autosomes into the "newly" created sex chromosomes.

"You started with an ancestral gene in flies and worms that was required for spermatogenesis. That then got duplicated in higher animals. And then very recently in Old World monkeys and humans, there was a duplication onto the Y, and that Y gene itself was multiply duplicated," says Steven A. Wassermen, PhD, professor of biology at the University of California at San Diego. "What appears to have happened in humans in particular is that you moved these genes onto the Y chromosome that are responsible for spermatogenesis and therefore subject to sexual selection.

Girl Power

According to Page, about half of the genes found on the Y chromosome are expressed -- that is, become active -- in the making of sperm in the testicles.

"It turns out there's a medical consequence of this," Page says. "It turns out that the most common known cause of spermatogenic failure, of male infertility, is deletion, is the absence of a part of the Y chromosome. There are various parts of the Y chromosome, [and] dropping out any one of those sections will shut down sperm production. These are common causes of spermatogenic failure in human populations."

But here's the kicker that may bruise a few fragile male egos, says Wang: It turns out that the Y chromosome is only part of the story. He discovered that in mice and men, the X chromosome actually seems to carry about 10 genes that are important in determining the production of primitive cells that in the developing embryo that will later determine sperm production or its absence. That's about three sperm-making genes on the "female" chromosome for every one on the male.

"This changes our way of thinking: Before, everyone in this field thought that the Y chromosome plays a very important role in spermatogenesis, if not a monopoly, but nobody thought about the X chromosome," Wang tells WebMD. "These findings change that completely: X chromosome not only plays a role, it looks like it plays the most important role."

Yet while all this may be somewhat counterintuitive, it's actually good news, because it opens up new avenues for investigation, says a researcher who specializes in male infertility.

"Genetic work is still in its early stages for whichever disease you're dealing with, and infertility is a disease state as well," says Erol Olen, MD, chief of the division of male infertility and sexual dysfunction at New England Medical Center in Boston. "Right now, it's more for education, more to let the patients know that, 'Looking at your genes, it's very unlikely that we'll recover sperm if we do some sort of intervention.' But ideally, this is something where in the future we'll be able to say, 'Well, these genes don't seem to be producing any signals, and if we can give you this or that and somehow turn them on, we might be able to increase spermatogenesis that way."


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