Understanding Male Infertility

Women, it seems, can't stop talking about fertility issues. Thousands of Web sites, groups and forums exist for women to discuss conception problems. But a quick Google search reveals few comparable resources for men to discuss the same subject, even though male infertility plays a role in about half of all infertility cases (about 15 percent of couples have difficulty conceiving).

But experts say that male infertility is surrounded by more social stigma, making it difficult for men to openly discuss or seek treatment. Even when a man seeks help, doctors say it's more difficult to diagnose and treat male infertility because the causes are often unapparent, tied to a particular enzyme or protein rather than an obvious anatomical problem.

"There's a relatively limited number of tools that we can actually use to treat male infertility," says Ricardo Azziz, the chair of obstetrics and gynecology at Cedars-Sinai Hospital in Los Angeles, who specializes in reproductive endocrinology and infertility.

A study published today in Nature may change that. Researchers at University of North Carolina have identified a gene in mice that's essential to the formation of functional sperm cells. When the gene is missing, it can cause sperm to form abnormally, making them unable to penetrate eggs. Azziz calls this work "an example of the future wave of research in male infertility."

The new research sheds light on how sperm become infertile at a basic, genetic level. As the sperm cells mature, they must go through a number of molecular steps, like assembly of the sperm tail and packaging of DNA. In the final step, spermiogenesis, the DNA coils in the sperm's head. What this new research shows is that a certain gene, called Jhdm2a, triggers the DNA to coil correctly in mice, creating a shape that can penetrate the egg. When mice lacked this gene, they created fewer mature sperm and the cells they did produce were largely infertile, with abnormally shaped heads and immobile tails.

"It's important because it shows that one of the mechanisms might rest on abnormal action of this particular enzyme" that's created by the Jhdm2a gene, says Azziz. Since this research comes from mice, researchers now must look at how common the Jhdm2a defect is in human males and what other cellular processes might be at play in order in to understand the therapeutic role this research could have.

Still, this new insight opens the possibility of treating male infertility with genetic therapy, where doctors could plausibly target particular genes, like Jhdm2a, in order to restore normal sperm function. A new treatment that alters sperm shape and count could have wide applicability in male infertility treatment as those factors account for about 40 percent of cases. This would be a welcome addition to the three treatments now used for male infertility: assisted reproduction, like in-vitro fertilization; surgery to remove varicose veins in the penis or testes, and drug therapy to correct a hormonal imbalance. Success rates are relatively low for these treatments; assisted reproductive technology, for example, has a success rate that hovers around 50 percent.
One of the most challenging obstacles to treating male infertility, however, may not even be medical. The social stigma that exists around male infertility deters men from seeking out treatment in the first place. In surveys, men report feeling "emasculated" or like "losers." Research like this, which gets to the serious science of male infertility, may help dispel such associations.

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