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 |
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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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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.</description><identifier>ISSN: 1470-1626</identifier><identifier>EISSN: 1741-7899</identifier><identifier>DOI: 10.1530/REP-12-0050</identifier><identifier>PMID: 22696190</identifier><language>eng</language><publisher>England: BioScientifica</publisher><subject>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</subject><ispartof>Reproduction (Cambridge, England), 2012-08, Vol.144 (2), p.187-193</ispartof><rights>2012 Society for Reproduction and Fertility</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b467t-bf7134352b2736bd8898e17ad87cc2eccae01cece9587f6fd25b62f12041d3ba3</citedby><cites>FETCH-LOGICAL-b467t-bf7134352b2736bd8898e17ad87cc2eccae01cece9587f6fd25b62f12041d3ba3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22696190$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kiyosu, Chiyo</creatorcontrib><creatorcontrib>Tsuji, Takehito</creatorcontrib><creatorcontrib>Yamada, Kaoru</creatorcontrib><creatorcontrib>Kajita, Shimpei</creatorcontrib><creatorcontrib>Kunieda, Tetsuo</creatorcontrib><title>NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation during follicular development in the mouse ovary</title><title>Reproduction (Cambridge, England)</title><addtitle>Reproduction</addtitle><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.</description><subject>Animals</subject><subject>Cell Cycle Checkpoints - genetics</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Shape - genetics</subject><subject>Cumulus Cells - metabolism</subject><subject>Cumulus Cells - physiology</subject><subject>Female</subject><subject>Fertility - genetics</subject><subject>Fertility - physiology</subject><subject>Meiosis - genetics</subject><subject>Meiosis - physiology</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Natriuretic Peptide, C-Type - metabolism</subject><subject>Natriuretic Peptide, C-Type - physiology</subject><subject>Oocytes - cytology</subject><subject>Oocytes - metabolism</subject><subject>Oocytes - physiology</subject><subject>Ovarian Follicle - metabolism</subject><subject>Ovarian Follicle - physiology</subject><subject>Ovary - cytology</subject><subject>Ovary - metabolism</subject><subject>Ovary - physiology</subject><subject>Ovary - ultrastructure</subject><subject>Receptors, Atrial Natriuretic Factor - genetics</subject><subject>Receptors, Atrial Natriuretic Factor - metabolism</subject><subject>Receptors, Atrial Natriuretic Factor - physiology</subject><issn>1470-1626</issn><issn>1741-7899</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1LxDAQhoMofp-8S46CVJO0TdKjLOsHiC6i55Kmk91I2qxJu7B_wV9tllWPepo5PDzMOy9CZ5Rc0TIn1y_TWUZZRkhJdtAhFQXNhKyq3bQXgmSUM36AjmJ8J4SWUvB9dMAYrzityCH6fJrNJtdPsxeGo533ytl-jm3EECP0g1UOGx-w93o9AO7A-sFqrEKAOGDVt1iP3ejGmIjlwoe0JLxTg_U9bsewkRnvnNWjUwG3sALnl10yY9vjYZGUfoyA_UqF9QnaM8pFOP2ex-jtdvo6uc8en-8eJjePWVNwMWSNETQv8pI1TOS8aaWsJFChWim0ZqC1AkI1aKhSWMNNy8qGM0MZKWibNyo_Rhdb7zL4jzEFqTsbNTinekjX1LTkXOaSlNX_KGFC5iy9PKGXW1QHH2MAUy-D7VKsBNWbnurUU01Zvekp0eff4rHpoP1lf4pJAN0CjfVR200Xxmr1p_QLJNygSg</recordid><startdate>201208</startdate><enddate>201208</enddate><creator>Kiyosu, Chiyo</creator><creator>Tsuji, Takehito</creator><creator>Yamada, Kaoru</creator><creator>Kajita, Shimpei</creator><creator>Kunieda, Tetsuo</creator><general>BioScientifica</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>201208</creationdate><title>NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation during follicular development in the mouse ovary</title><author>Kiyosu, Chiyo ; Tsuji, Takehito ; Yamada, Kaoru ; Kajita, Shimpei ; Kunieda, Tetsuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b467t-bf7134352b2736bd8898e17ad87cc2eccae01cece9587f6fd25b62f12041d3ba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Cell Cycle Checkpoints - genetics</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Shape - genetics</topic><topic>Cumulus Cells - metabolism</topic><topic>Cumulus Cells - physiology</topic><topic>Female</topic><topic>Fertility - genetics</topic><topic>Fertility - physiology</topic><topic>Meiosis - genetics</topic><topic>Meiosis - physiology</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Natriuretic Peptide, C-Type - metabolism</topic><topic>Natriuretic Peptide, C-Type - physiology</topic><topic>Oocytes - cytology</topic><topic>Oocytes - metabolism</topic><topic>Oocytes - physiology</topic><topic>Ovarian Follicle - metabolism</topic><topic>Ovarian Follicle - physiology</topic><topic>Ovary - cytology</topic><topic>Ovary - metabolism</topic><topic>Ovary - physiology</topic><topic>Ovary - ultrastructure</topic><topic>Receptors, Atrial Natriuretic Factor - genetics</topic><topic>Receptors, Atrial Natriuretic Factor - metabolism</topic><topic>Receptors, Atrial Natriuretic Factor - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kiyosu, Chiyo</creatorcontrib><creatorcontrib>Tsuji, Takehito</creatorcontrib><creatorcontrib>Yamada, Kaoru</creatorcontrib><creatorcontrib>Kajita, Shimpei</creatorcontrib><creatorcontrib>Kunieda, Tetsuo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Reproduction (Cambridge, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kiyosu, Chiyo</au><au>Tsuji, Takehito</au><au>Yamada, Kaoru</au><au>Kajita, Shimpei</au><au>Kunieda, Tetsuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation during follicular development in the mouse ovary</atitle><jtitle>Reproduction (Cambridge, England)</jtitle><addtitle>Reproduction</addtitle><date>2012-08</date><risdate>2012</risdate><volume>144</volume><issue>2</issue><spage>187</spage><epage>193</epage><pages>187-193</pages><issn>1470-1626</issn><eissn>1741-7899</eissn><abstract>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.</abstract><cop>England</cop><pub>BioScientifica</pub><pmid>22696190</pmid><doi>10.1530/REP-12-0050</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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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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