Contrary to long-standing scientific opinion, the female body doesn't put all of its eggs in one basket. A new study suggests that oocyte-depleted mouse ovaries may be replenished from stem cell reservoirs elsewhere in the body.

Recent years have seen dramatic challenges to some of the longest held beliefs in reproductive biology. “This field has been rooted in that concept that there's this fixed pool of eggs provided at birth,” explains Jonathan Tilly, a researcher at Massachusetts General Hospital (Boston, MA). “That concept's been, I think, fairly widely accepted for the better part of the past five decades.” It was thus a bit of a shock when, in 2004, Tilly's group presented evidence strongly supporting the continuous generation of new oocytes in the ovary throughout the mammalian reproductive life span. Their work built on earlier—but largely ignored—contrarian studies that suggest the existence of a reservoir of germline stem cells in the ovary.

But where have these cells been hiding? In a new study from Cell (29 July), Tilly's team presents a surprising possible answer. Initial experiments revealed a population of putative stem cells in the ovary, but their location and number—much too small for the scale of replenishment taking place—led Tilly's group to look for external sources. It immediately occurred to them that bone marrow (BM) stem cells were a strong candidate, because these cells have common lineage with primordial germ cells and are already known to replenish other organs, including the liver and heart. A number of transplantation experiments using recipient mice that have been chemically sterilized or are genetically incapable of producing mature oocytes seem to confirm this, showing that wild-type BM stem cells will rapidly differentiate to form a full spectrum of oocytes and follicles shortly after implantation. The authors suggest a model in which these stem cells may be transported by the peripheral blood to the ovarian medulla, where they can then mature into functioning oocytes and follicles.

Tilly's team is now working hard to confirm whether the oocytes generated from these BM stem cells are in fact fully fertile and functional. If they are, this could provide an important piece in a major puzzle of reproductive biology. Even if they aren't, though, this may not be the end of the story. “We think there still may be a role for these extranatal germ cells in supporting the ovaries through different means,” says Tilly. “You actually need far more oocytes than what's needed for fertility to make the tissue work...so it may be that these cells, in lieu of having any fertility, [are] there to support the tissue.”