NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation during follicular development in the mouse ovary

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 sig...

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Veröffentlicht in:Reproduction (Cambridge, England) England), 2012-08, Vol.144 (2), p.187-193
Hauptverfasser: Kiyosu, Chiyo, Tsuji, Takehito, Yamada, Kaoru, Kajita, Shimpei, Kunieda, Tetsuo
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container_title Reproduction (Cambridge, England)
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creator Kiyosu, Chiyo
Tsuji, Takehito
Yamada, Kaoru
Kajita, Shimpei
Kunieda, Tetsuo
description 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/Npr2cn female mice ovulated a comparable number of oocytes as normal mice but never produced a litter; ii) all ovulated oocytes of Npr2cn/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 Nppclbab/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.
doi_str_mv 10.1530/REP-12-0050
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We found that: i) Npr2cn/Npr2cn female mice ovulated a comparable number of oocytes as normal mice but never produced a litter; ii) all ovulated oocytes of Npr2cn/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 Nppclbab/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. 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ispartof Reproduction (Cambridge, England), 2012-08, Vol.144 (2), p.187-193
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subjects Animals
Cell Cycle Checkpoints - genetics
Cell Differentiation - genetics
Cell Shape - genetics
Cumulus Cells - metabolism
Cumulus Cells - physiology
Female
Fertility - genetics
Fertility - physiology
Meiosis - genetics
Meiosis - physiology
Mice
Mice, Transgenic
Natriuretic Peptide, C-Type - metabolism
Natriuretic Peptide, C-Type - physiology
Oocytes - cytology
Oocytes - metabolism
Oocytes - physiology
Ovarian Follicle - metabolism
Ovarian Follicle - physiology
Ovary - cytology
Ovary - metabolism
Ovary - physiology
Ovary - ultrastructure
Receptors, Atrial Natriuretic Factor - genetics
Receptors, Atrial Natriuretic Factor - metabolism
Receptors, Atrial Natriuretic Factor - physiology
title NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation during follicular development in the mouse ovary
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