Stem cells in bone marrow replenish mouse ovaries

Previously unrecognized stem cells found in the bone marrow and blood of mice can “restock” a depleted ovary with new egg cells within weeks, according to new research published in this week’s issue of the journal Cell.

This finding provides direct evidence to overturn a long-held dogma in reproductive biology, that female mice generate egg cells only during fetal development and thus are born with a finite stock of eggs that declines throughout life. The new report significantly extends earlier work from the same research team reporting the first preliminary evidence that ovaries of mice can be renewed with new eggs in adulthood.

The new study suggests an unexpected source for the progenitor cells that can jumpstart new egg cell production–outside of the ovary–say Jonathan Tilly and colleagues at Massachusetts General Hospital and Harvard Medical School.

The finding is “really revolutionizing how we think about female reproductive function,” Tilly says.

With the help of several genetic markers that are found in germ cells, the master cells that eventually give rise to the egg and sperm, the team shows evidence for the existence of germ cell progenitors, putative stem cells, in mouse bone marrow and blood. In addition, the researchers also found these markers in human bone marrow and blood.

Remarkably, the researchers found that bone marrow or blood cell transplants appear to completely revive the ovaries of female mice sterilized by chemotherapy. Just 24 hours after a transplant, the sterilized mice had new egg cells and follicles, the nurturing group of cells that encloses each egg cell. Two months after bone marrow transplant, the ovaries of normal mice and mice that had undergone chemotherapy appeared nearly identical, Tilly and colleagues discovered.

Expression of a germ cell marker in bone marrow fluctuated regularly with the female mouse’s estrous cycle, much like the cyclical rise and fall of certain hormones. Further results suggest that the ovary itself is sending out a chemical signal to the bone marrow, readying the progenitor cells to travel to the ovary and restock its egg cell supply.

Although it is not yet clear whether the egg cells (oocytes) generated following bone marrow transplants can mature and be fertilized to give rise to viable mouse pups, the findings provide an important first step toward investigating such potential for restoring fertility. In addition, the findings open the door for future studies examining whether restoration of ovaries could postpone the hormonal effects of menopause and could represent an alternative to hormone replacement therapy. Finally, the researchers would like to find out whether these stem cells could be coaxed to produce eggs in the laboratory, potentially providing a new source of eggs for therapeutic cloning.