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X Marks the Spot for Male Fertility

Infertile? Blame Mom
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July 16, 2001 -- The poet Alexander Pope famously declared that "the proper study of mankind is man." But just what a man is depends on the definition you choose. Warrior? Not exclusively a male role anymore. Leader? Yes, but women are also leaders. Hunter-gatherer? Sorry, fellas, like the old TV commercial said, women can bring home the bacon and fry it up in a pan.

So that pretty much leaves biology. Thank goodness we can still count on the old sex chromosomes, Ms. X and Mr. Y, can't we? Sure, the X chromosome has nearly 3,000 genes on it, compared with a measly two or three dozen on the Y chromosome. But you still need a Y to make a guy, right? Technically, yes, but it seems that even here there's some disagreement.

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The Mysteries of Maleness

The Human Genome Project is beginning to reveal some rather surprising clues into the role the Y chromosome has played over time, and now there's evidence to suggest that the X chromosome may also play a key role in the development of sperm. In fact, says Jeremy Wang, PhD, with the Whitehead Institute for Biomedical Research in Cambridge, Mass., some cases of male infertility may turn out to be X-chromosome-linked disorders transmitted from mothers to sons.

"This is like color-blindness, hemophilia -- those are X-linked disorders; the defect is passed on by the mother. So it's possible that male infertility could be passed on by the mother. The mother has one defective gene, the other is on the Y type [contributed by the father's sperm], and it could be passed on to her son, and her sons are infertile," says Wang, a postdoctoral fellow in the laboratory of David Page, MD, professor of Biology at the Massachusetts Institute of Technology and investigator at the Howard Hughes Medical Institute at the Whitehead, which is affiliated with MIT.

Page and colleagues have been playing gene detective, tracing through the 300-million-year history of the Y chromosome in search of clues to the mysteries of maleness, reproduction, and infertility, and what they found is enough to turn inside out the conventional thinking about gender and the contributions of mother and father.

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