Spindle assembly checkpoint-related failure perturbs early embryonic divisions and reduces reproductive performance of LT/Sv mice.
The phenotype of the LT/Sv strain of mice is manifested by abnormalities in oocyte meiotic cell-cycle, spontaneous parthenogenetic activation, teratomas formation, and frequent occurrence of embryonic triploidy. These abnormalities lead to the low rate of reproductive success. Recently, metaphase I arrest of LT/Sv oocytes has been attributed to the inability to timely inactivate the spindle assembly checkpoint (SAC). As differences in meiotic and mitotic SAC functioning were described, it remains obscure whether this abnormality is limited to the meiosis or also impinges on the mitotic divisions of LT/Sv embryos. Here, we show that a failure to inactivate SAC affects mitoses during preimplantation development of LT/Sv embryos. This is manifested by the prolonged localization of MAD2L1 on kinetochores of mitotic chromosomes and abnormally lengthened early embryonic M-phases. Moreover, LT/Sv embryos exhibit elevated frequency of abnormal chromosome separation during the first mitotic division. These abnormalities participate in severe impairment of preimplantation development and significantly decrease the reproductive success of this strain of mice. Thus, the common meiosis and mitosis SAC-related failure participates in a complex LT/Sv phenotype.
Maciejewska
Zuzanna
Z
Department of Embryology, Institute of Zoology, Faculty of Biology, University of Warsaw, Warsaw, Poland.
Polanski
Zbigniew
Z
Kisiel
Katarzyna
K
Kubiak
Jacek Z
JZ
Ciemerych
Maria A
MA
D000818:Animals; D001755:Blastocyst / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002869:Chromosome Aberrations; D020090:Chromosome Segregation; D046149:Embryo Culture Techniques; D005260:Female; D005307:Fertilization in Vitro; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics; D064246:Mad2 Proteins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D018613:Microscopy, Confocal; D018715:Microscopy, Video; D008938:Mitosis / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D054315:Oocyte Retrieval; D009865:Oocytes / Q000473:pathology; D010062:Ovulation Induction; D010312:Parthenogenesis; D010641:Phenotype; D011247:Pregnancy; D012098:Reproduction / Q000235:genetics; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
D018797:Cell Cycle Proteins; D064246:Mad2 Proteins; C577698:Mad2l1 protein, mouse; D009687:Nuclear Proteins