Stem cells and female reproduction: lessons from an unexpected source

The recent findings by Jonathon Tilly’s group at Harvard Medical School, show that female mice produce stem cells that give rise to eggs. This result overturns previous notions about mammalian reproduction, which held that females are born with all the eggs that they will ever have and that the decline in egg quality that occurs after a certain age is due to an extended aging process. What mammalian research has not been able to address at this point, however, is how these stem cells operate, what prompts them to develop into eggs, and why they are eventually lost. To answer these questions we must turn to our cousin the fruitfly.

“Most people don’t realize that the tiny fruitfly shares many genes and basic biological processes with us,” remarked Dr. Allan Spradling of the Carnegie Institution in Baltimore and author of Nature’s “News and Views” commenting on the Harvard work. “Female fruitflies remain fertile throughout their adult lives because they never lose all the stems cells from their ovaries. How these stem cells function and survive has been extensively studied. I believe that what we’ve learned from the fruitfly will help drive further research into mammalian reproductive stem cells and ultimately help us understand what leads to infertility, why menopause occurs, and whether we can figure out ways for these stem cells to be maintained longer.”

A world leader in the study of frutifly reproductive stem cells, called germline stem cells, Spradling explained: “Work in my lab and in the groups of three of my co-workers, Dr. Dennis McKearin of UT Southwestern, Dr. Haifan Lin, of Duke University, and Dr. Ting Xie of the Stowers Institute, have defined a small number of key factors that control how long germline stem cells continue to function. First, stem cells must interact with a particular type of somatic—or body—cell, which constantly sends it a signaling factor. Without this cell partner or its factor, the stem cells differentiate and are lost, while with excess factor they can last longer. Furthermore, we know that after a stem cell has been lost, a remaining stem cell will normally divide and repopulate its site or ‘niche.’ These two processes help ensure that fruitfly females do not run out of reproductive stem cells, despite a tendency for individual stem cells to turn over. It will be important to learn if mammalian germline stem cells utilize either of these mechanisms."