Nature 428, 145-150 (11 March 2004) | doi:10.1038/nature02316; Received 11 September 2003; Accepted 23 December 2003

Germline stem cells and follicular renewal in the postnatal mammalian ovary

Joshua Johnson1,2, Jacqueline Canning1,2, Tomoko Kaneko1, James K. Pru1 & Jonathan L. Tilly1

  1. Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital, and Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, Massachusetts 02114, USA
  2. These authors contributed equally to this work

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A basic doctrine of reproductive biology is that most mammalian females lose the capacity for germ-cell renewal during fetal life, such that a fixed reserve of germ cells (oocytes) enclosed within follicles is endowed at birth. Here we show that juvenile and adult mouse ovaries possess mitotically active germ cells that, based on rates of oocyte degeneration (atresia) and clearance, are needed to continuously replenish the follicle pool. Consistent with this, treatment of prepubertal female mice with the mitotic germ-cell toxicant busulphan eliminates the primordial follicle reserve by early adulthood without inducing atresia. Furthermore, we demonstrate cells expressing the meiotic entry marker synaptonemal complex protein 3 in juvenile and adult mouse ovaries. Wild-type ovaries grafted into transgenic female mice with ubiquitous expression of green fluorescent protein (GFP) become infiltrated with GFP-positive germ cells that form follicles. Collectively, these data establish the existence of proliferative germ cells that sustain oocyte and follicle production in the postnatal mammalian ovary.


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