File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Inhibitory phosphorylation of Cdk1 mediates prolonged prophase I arrest in female germ cells and is essential for female reproductive lifespan

TitleInhibitory phosphorylation of Cdk1 mediates prolonged prophase I arrest in female germ cells and is essential for female reproductive lifespan
Authors
Keywordsmeiotic prophase I
Cdk1 inhibitory phosphorylation
female fertility lifespan
immature oocyte
Issue Date2016
Citation
Cell Research, 2016, v. 26, n. 11, p. 1212-1225 How to Cite?
Abstract© 2016 IBCB, SIBS, CAS. A unique feature of female germ cell development in mammals is their remarkably long arrest at the prophase of meiosis I, which lasts up to 50 years in humans. Both dormant and growing oocytes are arrested at prophase I and completely lack the ability to resume meiosis. Here, we show that the prolonged meiotic arrest of female germ cells is largely achieved via the inhibitory phosphorylation of Cdk1 (cyclin-dependent kinase 1). In two mouse models where we have introduced mutant Cdk1 T14AY15F which cannot be inhibited by phosphorylation (Cdk1AF) in small meiotically incompetent oocytes, the prophase I arrest is interrupted, leading to a premature loss of female germ cells. We show that in growing oocytes, Cdk1AF leads to premature resumption of meiosis with condensed chromosomes and germinal vesicle breakdown followed by oocyte death, whereas in dormant oocytes, Cdk1AF leads to oocyte death directly, and both situations damage the ovarian reserve that maintains the female reproductive lifespan, which should be around 1 year in mice. Furthermore, interruption of the inhibitory phosphorylation of Cdk1 results in DNA damage, which is accompanied by induction of the Chk2 (checkpoint kinase 2)-p53/p63-dependent cell death pathway, which eventually causes global oocyte death. Together, our data demonstrate that the phosphorylation-mediated suppression of Cdk1 activity is one of the crucial factors that maintain the lengthy prophase arrest in mammalian female germ cells, which is essential for preserving the germ cell pool and reproductive lifespan in female mammals.
Persistent Identifierhttp://hdl.handle.net/10722/265501
ISSN
2023 Impact Factor: 28.1
2023 SCImago Journal Rankings: 9.506
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorAdhikari, Deepak-
dc.contributor.authorBusayavalasa, Kiran-
dc.contributor.authorZhang, Jingjing-
dc.contributor.authorHu, Mengwen-
dc.contributor.authorRisal, Sanjiv-
dc.contributor.authorBayazit, Mustafa Bilal-
dc.contributor.authorSingh, Meenakshi-
dc.contributor.authorDiril, M. Kasim-
dc.contributor.authorKaldis, Philipp-
dc.contributor.authorLiu, Kui-
dc.date.accessioned2018-12-03T01:20:51Z-
dc.date.available2018-12-03T01:20:51Z-
dc.date.issued2016-
dc.identifier.citationCell Research, 2016, v. 26, n. 11, p. 1212-1225-
dc.identifier.issn1001-0602-
dc.identifier.urihttp://hdl.handle.net/10722/265501-
dc.description.abstract© 2016 IBCB, SIBS, CAS. A unique feature of female germ cell development in mammals is their remarkably long arrest at the prophase of meiosis I, which lasts up to 50 years in humans. Both dormant and growing oocytes are arrested at prophase I and completely lack the ability to resume meiosis. Here, we show that the prolonged meiotic arrest of female germ cells is largely achieved via the inhibitory phosphorylation of Cdk1 (cyclin-dependent kinase 1). In two mouse models where we have introduced mutant Cdk1 T14AY15F which cannot be inhibited by phosphorylation (Cdk1AF) in small meiotically incompetent oocytes, the prophase I arrest is interrupted, leading to a premature loss of female germ cells. We show that in growing oocytes, Cdk1AF leads to premature resumption of meiosis with condensed chromosomes and germinal vesicle breakdown followed by oocyte death, whereas in dormant oocytes, Cdk1AF leads to oocyte death directly, and both situations damage the ovarian reserve that maintains the female reproductive lifespan, which should be around 1 year in mice. Furthermore, interruption of the inhibitory phosphorylation of Cdk1 results in DNA damage, which is accompanied by induction of the Chk2 (checkpoint kinase 2)-p53/p63-dependent cell death pathway, which eventually causes global oocyte death. Together, our data demonstrate that the phosphorylation-mediated suppression of Cdk1 activity is one of the crucial factors that maintain the lengthy prophase arrest in mammalian female germ cells, which is essential for preserving the germ cell pool and reproductive lifespan in female mammals.-
dc.languageeng-
dc.relation.ispartofCell Research-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectmeiotic prophase I-
dc.subjectCdk1 inhibitory phosphorylation-
dc.subjectfemale fertility lifespan-
dc.subjectimmature oocyte-
dc.titleInhibitory phosphorylation of Cdk1 mediates prolonged prophase I arrest in female germ cells and is essential for female reproductive lifespan-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/cr.2016.119-
dc.identifier.pmid27767095-
dc.identifier.scopuseid_2-s2.0-84992111018-
dc.identifier.volume26-
dc.identifier.issue11-
dc.identifier.spage1212-
dc.identifier.epage1225-
dc.identifier.eissn1748-7838-
dc.identifier.isiWOS:000387885300008-
dc.identifier.issnl1001-0602-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats