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Science 330 (6002): 366-369

Copyright © 2010 by the American Association for the Advancement of Science

Granulosa Cell Ligand NPPC and Its Receptor NPR2 Maintain Meiotic Arrest in Mouse Oocytes

Meijia Zhang,1,2 You-Qiang Su,2 Koji Sugiura,2,* Guoliang Xia,1,{dagger} John J. Eppig2,{dagger}

Abstract: Granulosa cells of mammalian Graafian follicles maintain oocytes in meiotic arrest, which prevents their precocious maturation. We show that mouse mural granulosa cells, which line the follicle wall, express natriuretic peptide precursor type C (Nppc) messenger RNA (mRNA), whereas cumulus cells surrounding oocytes express mRNA of the NPPC receptor NPR2, a guanylyl cyclase. NPPC increased cGMP levels in cumulus cells and oocytes and inhibited meiotic resumption in vitro. Meiotic arrest was not sustained in most Graafian follicles of Nppc or Npr2 mutant mice, and meiosis resumed precociously. Oocyte-derived paracrine factors promoted cumulus cell expression of Npr2 mRNA. Therefore, the granulosa cell ligand NPPC and its receptor NPR2 in cumulus cells prevent precocious meiotic maturation, which is critical for maturation and ovulation synchrony and for normal female fertility.

1 State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, People’s Republic of China.
2 The Jackson Laboratory, Bar Harbor, ME 04609, USA.

* Present address: Laboratory of Applied Genetics, Graduate School of Agricultural and Life Science, University of Tokyo, Tokyo, Japan.

{dagger} To whom correspondence should be addressed. E-mail: john.eppig{at}jax.org (J.J.E.); glxia{at}cau.edu.cn (G.X.)

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