"If these findings hold up in humans, all theories about the aging of the female reproductive system will have to be revisited," says Jonathan Tilly, PhD, of the Vincent Center for Reproductive Biology at MGH, the paper's lead author. "We also may need to revisit the mechanisms underlying such environmental effects on fertility as smoking, chemotherapy and radiation. Eventually this could lead to totally new approaches to combating infertility in cancer patients and others." Tilly is an associate professor of Obstetrics, Gynecology and Reproductive Biology at Harvard Medical School.
For several years Tilly's group has been studying the mechanisms behind the death of oocytes and follicles, the tiny sacs in which the eggs grow. In both mice and humans, the vast majority of oocytes are destined to die through a process called programmed cell death or apoptosis, the body's natural way of eliminating unneeded or damaged cells. The team's earlier research confirmed that oocytes destroyed by chemotherapy drugs or radiation also die through apoptosis, opening the possibility of designing ways to stop ovarian damage in female cancer patients and perhaps to postpone normal ovarian failure. However, to provide an essential context to their efforts to inhibit oocyte apoptosis, the researchers decided to measure the numbers of healthy and dying follicles in mouse ovaries through the animals' lifespan.