A Gene Behind Both Infertility and Contraception

Study finds it controls regular release of eggs

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HealthDay Reporter

(HealthDay is the new name for HealthScoutNews.)

THURSDAY, July 10, 2003 (HealthDayNews) -- Researchers have discovered a gene that could play a part in helping both women who want to have children and those who don't -- and it might help fight cancer, to boot.

The gene plays a central role in a network that controls the periodic release of eggs for fertilization, says a report in the July 11 issue of Science by researchers at Harvard's Dana-Farber Cancer Institute.

Female mice bred to lack the gene had fewer and smaller litters and were infertile after 15 weeks, which is equal to early adulthood for a woman. Detailed studies found the follicles -- segments of the ovary that contain eggs -- were activated earlier in life than normal and depleted earlier.

Activation means that one follicle of the many that a female carries changes from a resting phase to an active stage, maturing so the egg will be released. This activation process is controlled by a family of genes, and the one described in the latest study, dubbed FoXo3a, plays a vital role in that family.

So, the researchers say, the discovery could help women who are infertile because they experience the same early follicle failure seen in the mice. Turning the picture around, a drug that could delay follicular activation could be a useful contraceptive, keeping the eggs in storage until a woman decided the time had come to have a baby. Contraceptive pills prevent ovulation but do not slow the rate of activation, so eggs are gradually lost.

And since the same genetic pathway is implicated in aging and cancer, studying FoXo3a might give some clues to both, says a statement from study author Dr. Ronald A. DePinho. The work was done in DePinho's laboratory at the Dana-Farber Cancer Institute by Dr. Diego H. Castrillon, then a postdoctoral fellow.

About 1 percent of women have the kind of early failure of follicular function seen in the study, says Castrillon, who will soon become an assistant professor of pathology at the University of Texas Southwestern Medical Center in Dallas. While exact information is not available, it's believed "the majority of cases are due to this kind of follicular burnout," he says.

He says he will study the role of the FoXo3a gene in human infertility when he begins work in Texas. "This study is an example of how research can help frame new questions, open a line of investigation," Castrillon says. "This is a very important question that I and many other people will try to answer."

Development of a contraceptive based on the finding "is a long way off, but this is a first step," Castrillon says. "Understanding this pathway can help you do a lot of things by regulating the rate of follicular activation."

More information

Basic knowledge about infertility is available from the American Society of Reproductive Medicine or the National Infertility Association.

SOURCES: Diego H. Castrillon, M.D., Ph.D, assistant professor, pathology, University of Texas Southwestern Medical Center, Dallas; July 11, 2003, Science

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