Egg regeneration study opens fertility window

Current understanding of female reproductive biology may be revised with publication of new research that indicates that female mice retain the ability to make new egg cells well into adulthood.1 Scientists long have believed that female mammals are born with a finite supply of cells, known as oocytes, that are lost at a steady rate until the supply is exhausted. Such a process leads to menopause in women.

Researchers at the Boston-based Massachusetts General Hospital report that new oocyte-containing follicles continue to develop in the ovaries of adult mice.1 The research, supported by the federal National Institute on Aging, suggests that these new oocytes come from stem cells located in the ovary.1

"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, an associate professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, also in Boston and developmental biologist in the hospital’s Vincent Center for Reproductive Biology. "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."

The concept of egg regeneration will open a new area of research if the findings are supported by other studies and in other species as well, remarks Lee Lee Doyle, PhD, chairman of the board of directors of the Washington, DC-based Association of Reproductive Health Professionals (ARHP) and professor emeritus at the University of Arkansas for Medical Sciences in Little Rock.

The big issue is the "if," agrees Mitchell Creinin, MD, professor of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh School of Medicine and chairman of ARHP’s education committee.

"There is still a lot of work to be done to understand if these findings can be replicated by others, what they really mean, [and] is this true for humans," he observes.

Look at the findings

The mechanisms behind the death of oocytes and follicles has been the focus of the Boston-based research group.2 Scientists in the group have been seeking better ways to regulate cell death during chemotherapy and thus help protect fertility in cancer patients.3

The scientists began by comparing the numbers of healthy and degenerating follicles in the ovaries of a particular strain of mice from birth through young adulthood. They hypothesized that if the number of follicles in the ovary is set at or shortly after birth, then the loss of healthy follicles over time would be accounted for by the total number of follicles undergoing degeneration during the same time period. However, they found that the incidence of degenerating follicles was significantly greater than the loss over time of healthy follicles. With evidence that degenerating follicles disappeared from the ovaries within three days, scientists then deduced that the mouse ovaries continue to produce new oocyte-containing follicles into adulthood.4

The scientists replicated the same results in two other strains of mice, then went on to pinpoint the presence of large cells on the surface layer of cells in the mouse ovaries that they identified as germ cells. They also uncovered signs in adult animals of meiosis, the specialized cell division that only occurs in the formation of sex cells, which according to current thinking, should have been halted before birth.4

To further their research, the scientists transplanted ovarian tissue from adult wild-type mice into adult female mice developed to express a particular type of protein in their cells. When they examined the transplanted ovarian tissue under microscope, they found follicles housing the protein, which indicated new follicle production in the adult mice ovaries.4

Opening the door

When the 20th century began, some scholars suggested that eggs could be replenished in adult mammals; however, a 1951 study provided a definitive argument that egg numbers are determined at birth.5 Female reproductive biology has rested on that argument ever since.

If the latest discovery is confirmed in humans, that argument will be discarded and new therapies may be developed, such as transplanting ovarian stem cells for infertility.6

The Boston research group is attempting to isolate the ovarian stem cells from mice and identify characteristic active genes within them. Scientists then will search for potential stem cells with similar genetic signatures in biopsies of human ovaries.

References

1. Johnson J, Canning J, Kaneko T, et al. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 2004; 428:145-150.

2. McGreevey S. MGH study finds female mammals produce egg cells into adulthood. Press release. March 10, 2004. Web site: www.massgeneral.org/news/releases/031004tilly.html.

3. Angier N. Study of mice reproduction discovers egg regeneration. New York Times, March 11, 2004. Web site: www.nytimes.com/2004/03/11/science/11OVAR.html.

4. Kolsky K. New eggs continue to develop in adult mice. Press release. March 10, 2004. Web site: www.nih.gov/news/pr/mar2004/nia-10.htm.

5. Zuckerman, S. The number of oocytes in the mature ovary. Recent Progress in Hormone Research 1955; 6: 63-108.

6. Goldfarb B. Egg research lays big surprise. USA Today, March 10, 2004. Web site: www.usatoday.com/news/health/2004-03-10-egg-research-usat_x.htm.