Journal
SCIENCE
Volume 330, Issue 6002, Pages 366-369Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1193573
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Funding
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD23839, HD21970]
- National Basic Research Program of China [2007CB947401, 2006CB504003]
- State Key Laboratory for Agrobiotechnology of China [2009SKLAB07-5]
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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.
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