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Germline stem cells and follicular renewal in the postnatal mammalian ovary

Nature volume 428, pages 145150 (11 March 2004) | Download Citation

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  • A Corrigendum to this article was published on 26 August 2004

Abstract

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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Acknowledgements

We thank Y. Morita for technical assistance; T. Noce for MVH antiserum; T. Ashley for SCP3 antiserum; and I. Schiff and F. Frigoletto Jr for critical reading of the manuscript before its submission. This work was supported by the National Institute on Aging and by Vincent Memorial Research Funds. This study was conducted while J.L.T. was an Investigator of the Steven and Michele Kirsch Foundation, and while J.J. was a Research Fellow supported by The Lalor Foundation.

Author information

Author notes

    • Joshua Johnson
    •  & Jacqueline Canning

    These authors contributed equally to this work

Affiliations

  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

    • Joshua Johnson
    • , Jacqueline Canning
    • , Tomoko Kaneko
    • , James K. Pru
    •  & Jonathan L. Tilly

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Competing interests

The authors declare that they have no competing financial interests.

Corresponding author

Correspondence to Jonathan L. Tilly.

Supplementary information

Word documents

  1. 1.

    Supplementary Information

    This includes supplementary methods and supplementary figure legends.

Image files

  1. 1.

    Supplementary Figure 1

    Grafted wild-type ovarian tissue adheres to transgenic host ovarian tissue and becomes vascularized.

  2. 2.

    Supplementary Figure 2

    Wild-type ovarian tissue exhibits a low level of background autofluorescence.

  3. 3.

    Supplementary Figure 3

    Additional example of folliculogenesis in grafted ovarian tissue.

  4. 4.

    Supplementary Figure 4

    Postnatal ovarian expression of stem cell-associated genes.

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DOI

https://doi.org/10.1038/nature02316

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