PLoS ONE | Vol.6, Issue.6 | 2017-05-29 | Pages
Spindle assembly checkpoint regulates mitotic cell cycle progression during preimplantation embryo development.
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.
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Spindle assembly checkpoint regulates mitotic cell cycle progression during preimplantation embryo development.
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.
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chromatid embryos embryo death embryonic aneuploidy of mitotic cell cycle progression spindle assembly checkpoint sac development implantation formation chromosome misalignment mitotic fidelity abortion genetic diseases rna interference preimplantation distribution drug aneuploid embryo formation metaphaseanaphase transition
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Mo Li,Qing-hua ZHANG,Liang Wei,Cai-Rong Yang,Yanchang Wei,Yi Hou,Heide Schatten,Qing-Yuan Sun,Ying-Chun Ouyang,Saima Multi,Junyu Ma,Zhen-Bo Wang,Zhao-Jia Ge,Chun-Hui Zhang,.Spindle assembly checkpoint regulates mitotic cell cycle progression during preimplantation embryo development.. 6 (6),.
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