title: Chk2 regulates cell cycle progression during mouse oocyte maturation and early embryo development.
abstract: As a tumor suppressor homologue during mitosis, Chk2 is involved in replication checkpoints, DNA repair, and cell cycle arrest, although its functions during mouse oocyte meiosis and early embryo development remain uncertain. We investigated the functions of Chk2 during mouse oocyte maturation and early embryo development. Chk2 exhibited a dynamic localization pattern; Chk2 expression was restricted to germinal vesicles at the germinal vesicle (GV) stage, was associated with centromeres at pro-metaphase I (Pro-MI), and localized to spindle poles at metaphase I (MI). Disrupting Chk2 activity resulted in cell cycle progression defects. First, inhibitor-treated oocytes were arrested at the GV stage and failed to undergo germinal vesicle breakdown (GVBD); this could be rescued after Chk2 inhibition release. Second, Chk2 inhibition after oocyte GVBD caused MI arrest. Third, the first cleavage of early embryo development was disrupted by Chk2 inhibition. Additionally, in inhibitor-treated oocytes, checkpoint protein Bub3 expression was consistently localized at centromeres at the MI stage, which indicated that the spindle assembly checkpoint (SAC) was activated. Moreover, disrupting Chk2 activity in oocytes caused severe chromosome misalignments and spindle disruption. In inhibitor-treated oocytes, centrosome protein γ-tubulin and Polo-like kinase 1 (Plk1) were dissociated from spindle poles. These results indicated that Chk2 regulated cell cycle progression and spindle assembly during mouse oocyte maturation and early embryo development.
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Xiao-Xin
authors.initials: XX
authors.lastname: Dai
authors.forename: Xing
authors.initials: X
authors.lastname: Duan
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Liu
authors.forename: Xiang-Shun
authors.initials: XS
authors.lastname: Cui
authors.forename: Nam-Hyung
authors.initials: NH
authors.lastname: Kim
authors.forename: Shao-Chen
authors.initials: SC
authors.lastname: Sun
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D064447:Checkpoint Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D033481:Chromosomes, Mammalian; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D008297:Male; D008540:Meiosis / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009865:Oocytes / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism*
chemical_list: C489445:Bub3 protein, mouse; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D000075223:Poly-ADP-Ribose Binding Proteins; D047428:Protein Kinase Inhibitors; D064447:Checkpoint Kinase 2; C578633:Chek2 protein, mouse