For most women, menopause occurs in their late 40s or early 50s. About 1 percent of women, however, experience menopause before the age of 40. Researchers have long known that radiation therapy, chemotherapy and certain autoimmune diseases can lead to early onset ovarian failure, as premature menopause is officially termed. Yet some 30 percent of women with the disorder have a female relative who is also affected, suggesting that in many cases premature menopause might have a genetic basis. Now new research, described in the February issue of Nature Genetics, has revealed for the first time a genetic mutation that appears to bring about early menopause. The mutation also produces an eyelid defect known as blepharophimosis in newborns. As such the discovery could help scientists understand how genetic processes that take place during fetal development can manifest at birth and later in life.
The newly identified gene, dubbed FOXL2, is a so-called transcription factor. That is, it activates or inactivates genes in the eyelids and ovaries at the appropriate times during development. Mutations in FOXL2 therefore disrupt the normal processes. The exact mechanism by which FOXL2 causes women to produce fewer eggs is still unknown, but it may be that mutant FOXL2 arrests normal egg follicle development or prompts some action that destroys the eggs.
"Although we're talking about an age-related condition, menopause, all of the critical events have occurred in fetal development that determine when menopause will occur," notes David Schlessinger of the National Institute on Aging, a co-author of the study. "If we understand more about how tissues are formed, we might be able to prolong the function of cells and even regenerate tissues that are worn out."