title: Spindle assembly checkpoint regulates mitotic cell cycle progression during preimplantation embryo development.
abstract: Errors in chromosome segregation or distribution may result in aneuploid embryo formation, which causes implantation failure, spontaneous abortion, genetic diseases, or embryo death. Embryonic aneuploidy occurs when chromosome aberrations are present in gametes or early embryos. To date, it is still unclear whether the spindle assembly checkpoint (SAC) is required for the regulation of mitotic cell cycle progression to ensure mitotic fidelity during preimplantation development. In this study, using overexpression and RNA interference (RNAi) approaches, we analyzed the role of SAC components (Bub3, BubR1 and Mad2) in mouse preimplantation embryos. Our data showed that overexpressed SAC components inhibited metaphase-anaphase transition by preventing sister chromatid segregation. Deletion of SAC components by RNAi accelerated the metaphase-anaphase transition during the first cleavage and caused micronuclei formation, chromosome misalignment and aneuploidy, which caused decreased implantation and delayed development. Furthermore, in the presence of the spindle-depolymerizing drug nocodazole, SAC depleted embryos failed to arrest at metaphase. Our results suggest that SAC is essential for the regulation of mitotic cell cycle progression in cleavage stage mouse embryos.
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors: Yanchang
authors: Y
authors: Wei
authors: Saima
authors: S
authors: Multi
authors: Cai-Rong
authors: CR
authors: Yang
authors: Junyu
authors: J
authors: Ma
authors: Qing-Hua
authors: QH
authors: Zhang
authors: Zhen-Bo
authors: ZB
authors: Wang
authors: Mo
authors: M
authors: Li
authors: Liang
authors: L
authors: Wei
authors: Zhao-Jia
authors: ZJ
authors: Ge
authors: Chun-Hui
authors: CH
authors: Zhang
authors: Ying-Chun
authors: YC
authors: Ouyang
authors: Yi
authors: Y
authors: Hou
authors: Heide
authors: H
authors: Schatten
authors: Qing-Yuan
authors: QY
authors: Sun
mesh_terms: D000705:Anaphase / Q000187:drug effects; D000782:Aneuploidy; D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002842:Chromatids / Q000187:drug effects / Q000378:metabolism; D020090:Chromosome Segregation / Q000187:drug effects; D033481:Chromosomes, Mammalian / Q000378:metabolism; D004624:Embryo Transfer; D047108:Embryonic Development / Q000187:drug effects; D008677:Metaphase / Q000187:drug effects; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D015739:Nocodazole / Q000494:pharmacology; D010641:Phenotype; D021381:Protein Transport / Q000187:drug effects; D034622:RNA Interference; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
chemical_list: D015739:Nocodazole