TY - JOUR
T1 - NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation during follicular development in the mouse ovary
AU - Kiyosu, Chiyo
AU - Tsuji, Takehito
AU - Yamada, Kaoru
AU - Kajita, Shimpei
AU - Kunieda, Tetsuo
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/8
Y1 - 2012/8
N2 - 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 Nppclbab or Npr2cn, 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) Npr2cn/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/Npr2cn and Nppclbab/Nppclbab 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 Npr2cn/Npr2cn and Nppc lbab/Nppclbab 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.
AB - 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 Nppclbab or Npr2cn, 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) Npr2cn/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/Npr2cn and Nppclbab/Nppclbab 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 Npr2cn/Npr2cn and Nppc lbab/Nppclbab 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.
UR - http://www.scopus.com/inward/record.url?scp=84864376924&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864376924&partnerID=8YFLogxK
U2 - 10.1530/REP-12-0050
DO - 10.1530/REP-12-0050
M3 - Article
C2 - 22696190
AN - SCOPUS:84864376924
VL - 144
SP - 187
EP - 193
JO - Reviews of Reproduction
JF - Reviews of Reproduction
SN - 1470-1626
IS - 2
ER -