title: Geminin deletion in mouse oocytes results in impaired embryo development and reduced fertility.
abstract: Geminin controls proper centrosome duplication, cell division, and differentiation. We investigated the function of geminin in oogenesis, fertilization, and early embryo development by deleting the geminin gene in oocytes from the primordial follicle stage. Oocyte-specific disruption of geminin results in low fertility in mice. Even though there was no evident anomaly of oogenesis, oocyte meiotic maturation, natural ovulation, or fertilization, early embryo development and implantation were impaired. The fertilized eggs derived from mutant mice showed developmental delay, and many were blocked at the late zygote stage. Cdt1 protein was decreased, whereas Chk1 and H2AX phosphorylation was increased, in fertilized eggs after geminin depletion. Our results suggest that disruption of maternal geminin may decrease Cdt1 expression and cause DNA rereplication, which then activates the cell cycle checkpoint and DNA damage repair and thus impairs early embryo development.
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xue-Shan
authors.initials: XS
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhong-Wei
authors.initials: ZW
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Meng-Wen
authors.initials: MW
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Tie-Gang
authors.initials: TG
authors.lastname: Meng
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zong-Zhe
authors.initials: ZZ
authors.lastname: Jiang
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211.
authors.forename: Heide
authors.initials: H
authors.lastname: Schatten
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China wangzhb00@hotmail.com sunqy@ioz.ac.cn.
authors.forename: Zhen-Bo
authors.initials: ZB
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China wangzhb00@hotmail.com sunqy@ioz.ac.cn.
authors.forename: Qing-Yuan
authors.initials: QY
authors.lastname: Sun
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics; D000071877:Checkpoint Kinase 1 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004622:Embryo, Mammalian / Q000502:physiology; D005260:Female; D005298:Fertility / Q000235:genetics*; D005306:Fertilization / Q000502:physiology; D064248:Geminin / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008297:Male; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009865:Oocytes / Q000502:physiology*; D009866:Oogenesis / Q000235:genetics; D010060:Ovulation / Q000235:genetics; D010766:Phosphorylation; D015053:Zygote / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D000071877:Checkpoint Kinase 1; D004268:DNA-Binding Proteins; D064248:Geminin; D006657:Histones; C577997:Gmnn protein, mouse; C498645:Ris2 protein, mouse; C000605869:Chek1 protein, mouse; C475961:gamma-H2AX protein, mouse