Gene Knockout Prolongs Ovarian Lifespan In Mice

A research team based at the Massachusetts General Hospital (MGH) has found that inactivation of a single gene in female mice can sustain ovarian function into advanced age. The report in the February issue of Nature Genetics describes how female mice in which a gene called Bax is inactivated do not experience the normal loss of ovarian cells that occurs throughout the animal' lifetime.

While these aged mice maintain a functioning supply of both oocytes (egg cells) and hormone-secreting granulosa cells, they do not ovulate or become pregnant under normal conditions. The research, which still is far from application in humans, may eventually lead to new techniques for delaying menopause and reducing its associated health risks.

"The Bax-deficient mice retained hundreds of ovarian follicles [tiny sacs containing an oocyte surrounded by granulosa cells] at an age when the ovaries are usually barren," says Jonathan Tilly, PhD, director of the MGH Vincent Center for Reproductive Biology and the paper's senior author. "And we were very pleased to find that the aged Bax-deficient mice appear to develop relatively normally in every other way."

Bax is one of a group of genes known to be key to programmed cell death -- the natural process by which unneeded cells are eliminated from the body. Previous research by the MGH-based team had shown that Bax expression was correlated with ovarian cell death in mice and humans. (Mammalian females are born with a set number of oocytes, more than 90 percent of which die off throughout the animal's lifetime.) Bax was first cloned by Stanley Korsmeyer, MD, a member of the research team who also produced the Bax-knockout mice. Korsmeyer was with the Howard Hughes Medical Institute at Washington University School of Medicine in St. Louis while this study was conducted and is now at the Dana-Farber Cancer Institute in Boston.

Pursuing the suggestion that inactivation of Bax could preserve ovarian cells, the res

Contact: Susan McGreevey
Massachusetts General Hospital

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