Graduate School of Natural Science and Technology, Okayama University, Tsushima-naka, Okayama 700-8530, Japan.
Reproduction. 2012 Aug;144(2):187-93. doi: 10.1530/REP-12-0050. Epub 2012 Jun 13.
Natriuretic peptide type C (NPPC) and its high affinity receptor, natriuretic peptide receptor 2 (NPR2), have been assumed to be involved in female reproduction and have recently been shown to play an essential role in maintaining meiotic arrest of oocytes. However, the overall role of NPPC/NPR2 signaling in female reproduction and ovarian function is still less clear. Here we report the defects observed in oocytes and follicles of mice homozygous for Nppc(lbab) or Npr2(cn), mutant alleles of Nppc or Npr2 respectively to clarify the exact consequences of lack of NPPC/NPR2 signaling in female reproductive systems. We found that: i) Npr2(cn)/Npr2(cn) female mice ovulated a comparable number of oocytes as normal mice but never produced a litter; ii) all ovulated oocytes of Npr2(cn)/Npr2(cn) and Nppc(lbab)/Nppc(lbab) mice exhibited abnormalities, such as fragmented or degenerated ooplasm and never developed to the two-cell stage after fertilization; iii) histological examination of the ovaries of Npr2(cn)/Npr2(cn) and Nppc(lbab)/Nppc(lbab) mice showed that oocytes in antral follicles prematurely resumed meiosis and that immediately before ovulation, oocytes showed disorganized chromosomes or fragmented ooplasm; and iv) ovulated oocytes and oocytes in the periovulatory follicles of the mutant mice were devoid of cumulus cells. These findings demonstrate that NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation, which affects female fertility through the production of oocytes with developmental capacity.
脑钠肽 C（NPPC）及其高亲和力受体，脑钠肽受体 2（NPR2），被认为参与雌性生殖，并最近被证明在维持卵母细胞减数分裂阻滞中发挥重要作用。然而，NPPC/NPR2 信号在雌性生殖和卵巢功能中的总体作用仍不太清楚。在这里，我们报道了 Nppc(lbab)或 Npr2(cn)杂合突变小鼠的卵母细胞和卵泡中观察到的缺陷，分别为 Nppc 或 Npr2 的突变等位基因，以阐明 NPPC/NPR2 信号缺失在雌性生殖系统中的确切后果。我们发现：i）Npr2(cn)/Npr2(cn)雌性小鼠排卵的卵母细胞数量与正常小鼠相当，但从未产下一窝；ii）Npr2(cn)/Npr2(cn)和 Nppc(lbab)/Nppc(lbab)小鼠所有排卵的卵母细胞都出现异常，如卵质碎片化或退化，受精后从未发育到二细胞阶段；iii）Npr2(cn)/Npr2(cn)和 Nppc(lbab)/Nppc(lbab)小鼠卵巢的组织学检查显示，窦卵泡中的卵母细胞过早地恢复减数分裂，并且在排卵前，卵母细胞显示染色体排列紊乱或卵质碎片化；iv）突变小鼠排卵的卵母细胞和促排卵卵泡中的卵母细胞缺乏卵丘细胞。这些发现表明，NPPC/NPR2 信号对于卵母细胞减数分裂阻滞和卵丘卵母细胞形成是必不可少的，这通过产生具有发育能力的卵母细胞来影响雌性生育能力。
