The investigators say the discovery will lead to unique animal models of premature ovarian failure (POF), or early menopause, useful for further studying the poorly understood condition.

POF, which is diagnosed in 1 in 100 women ages 30 to 39, results from the depletion of a woman's supply of eggs early in her reproductive years.

A report on the discovery is being published in the July 11 issue of Science. Lead author is Diego H. Castrillon, MD, PhD, a postdoctoral fellow in the laboratory of Ronald A. DePinho, MD, at Dana-Farber, where the work was done. DePinho is the senior author, and three other Dana-Farber researchers contributed to the paper.

Castrillon is a staff pathologist at BWH and will move to the University of Texas-Southwestern Medical School in September.

"This provides a molecular foothold into a process that we knew little about - that is, the mechanism that constrains or triggers the activation and maturation of the egg," says DePinho.

The findings grew out of an experiment in which the researchers created mice lacking both copies of the FOXO3a gene, which belongs to the forkhead gene family. As transcription regulators, or switches that turn other genes on and off, forkhead genes are believed to control processes related to aging, cancer and diabetes. In this experiment, the researchers "knocked out" the FOXO3a gene, effectively mutating it, in mice to observe the consequences.

As the gene-altered mice aged, the females were observed to have fewer and smaller litters, and by 15 weeks of age - comparable to early adulthood in a woman - they were sterile. Further study revealed that within the ovaries of mice lacking the FOXO3a gene, the follicl
'"/>

Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
10-Jul-2003