1. The Stowers Medical Institute, Harvard Stem Cell Institute and The Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
2. Section on Developmental and Stem Cell Biology, Joslin Diabetes Center and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02215, and Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA
3. Center for Reproductive Medicine and Infertility, Weill Medical College, Cornell University, New York, New York 10021, USA

Correspondence to: Amy J. Wagers² Correspondence and requests for materials should be addressed to A.J.W. (Email: amy.wagers@joslin.harvard.edu).

Abstract

Decades of research in reproductive biology have led to the generally accepted belief that in female mammals, all surviving germ cells enter meiosis at the end of fetal development and as a result, the postnatal ovary harbours a limited supply of oocytes that cannot be replenished or regenerated if lost to injury or disease. However, recent reports have challenged this view, suggesting instead that oocyte production is maintained through continual seeding of the ovary by circulating, bone-marrow-derived germ cells. To test directly the physiological relevance of circulating cells for female fertility, we established transplantation and parabiotic mouse models to assess the capacity of circulating bone marrow cells to generate ovulated oocytes, both in the steady state and after induced damage. Our studies showed no evidence that bone marrow cells, or any other normally circulating cells, contribute to the formation of mature, ovulated oocytes. Instead, cells that travelled to the ovary through the bloodstream exhibited properties characteristic of committed blood leukocytes.

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