Study Shows Female Mice Produce New Eggs

A new study by a Harvard medical researcher is challenging the long-held belief that female mammals are born with all the eggs they will produce in their lives.

The study, released last week by Dr. Jonathan Tilly of the Vincent Center for Reproductive Biology at Massachusetts General Hospital, involves the discovery of germ stem cells in the ovaries of adult mice.

If these findings prove to be true in humans as well, they would prompt a new assessment of female reproduction.

“If these results hold up in humans, this would change everything we read in our textbooks,” said Tilly, an associate professor of Obstetrics, Gynecology and Reproductive Biology at Harvard Medical School. “Eventually this could open up wide possibilities for menopause regulation and improved women’s health and allow wider reproductive options for women undergoing chemotherapy.”

Whereas men produce sperm cells throughout their lives in stem cells in their testes, women are thought to be born with a fixed number of eggs that are released between puberty and menopause.

In describing the currently accepted view, Tilly said that for human females, about 7 million eggs are produced during gestation and die off gradually over the course of a woman’s life. At birth a human female has 1 million eggs; by puberty she has only 300,000. About 400 eggs on average are released in a woman’s life; the remainder are destroyed by the body through a process of cell death, or apoptosis.

The existence of stem cells in mice, however, could indicate that menopause, or “mouse-opause,” as Tilly calls it, results not from the death of eggs, but from the gradual death of germ stem cells which produce these eggs.

This process is associated with aging in male mice as well. But, because every male has thousands of germ stem cells, as opposed to a female’s approximately 60, the decrease associated with aging is not sufficient to impair testicular functioning.

The existence of ovarian germ stem cells is known in flies and some fish and birds. Given his recent findings in mice, Tilly said, it would not be a stretch to believe that germ stem cells would have been an evolutionarily adaptive trait in human females as well.

Professor and Director of Reproductive Biology at the Yale Laboratory of Reproductive Biology Harold R. Behrman called Tilly’s work a “very significant” find that prompts a new look at the assumptions about human egg generation. “The dogma has been that mammalian eggs don’t regenerate after birth,” Behrman said.

Behrman expressed his excitement about the study, which has the potential to change these accepted beliefs, but cautioned that at this stage the study is “of questionable relevance to humans.” He noted that “it is clear that like all scientific studies this study has to be repeated by independent labs to determine its significance.”

Behrman also said it is too early to determine whether the results of the study could mean a longer period of fertility for women.

Professor of Cell and Developmental Biology at the University of Pennsylvania School of Medicine Stephen DiNardo said that Tilly’s results allow us to better understand how biological systems work.

“Regardless of whether the findings are applicable in humans, research on adult stem cells allows us to understand better how stem cells behave generally speaking,” DiNardo said. “This sort of research will ultimately have applications to human health as well.”

Recent findings indicate other promising avenues in human reproductive biology. Kutluk Oktay, associate professor of reproductive medicine and obstetrics and gynecology at Cornell’s Center for Reproductive Medicine and Infertility, recently announced that it is possible to freeze ovarian tissue for up to six months, replant it into a woman’s abdominal area and have it resume production of eggs. This finding has applications for women who are undergoing radiation treatment, which destroys egg cells.