颗粒细胞上的配体NPPC及其受体NPR2维持小鼠卵母细胞减数分裂的阻滞

哺乳动物卵泡中的颗粒细胞维持了卵母细胞处于减数分裂阻滞状态,这可以防止它们过早成熟。研究发现,位于卵泡壁上的颗粒细胞表达C-型钠肽(NPPC)的信使RNA;而卵母细胞周围的卵丘细胞表达NPPC受体NPR2的信使RNA,这是一个鸟苷酸环化酶。细胞培养实验显示,NPPC可增加卵丘细胞和卵母细胞中cGMP的表达水平,抑制了减数分裂的恢复。Nppc或Npr2突变小鼠,减数分裂阻滞将在大多数卵泡中不能持续,减数分裂得以提早恢复。卵母细胞源旁分泌因子可促使卵丘细胞表达Npr2的信使RNA。上述结果表明,颗粒细胞上的配体NPPC及其卵丘细胞上的受体NPR2协同防止了减数分裂的过早成熟,这对于成熟和排卵的协调以及对于雌性生殖都至关重要。

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

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.