Inhibition of survivin induces spindle disorganization, chromosome misalignment, and DNA damage during mouse embryo development

Abstract

ABSTRACT The early embryonic development is important for the subsequent embryo implantation, and any defects in this process can lead to embryonic aneuploidy, which causes miscarriage and birth defects. Survivin is the member of inhibitor of apoptosis protein (IAP) family, and it is also an essential subunit of chromosomal passenger complex (CPC), which regulates both apoptosis and cell cycle control in many models. However, the roles of survivin in mouse early embryos remain unclear. In the present study, we showed that survivin activity was essential for mouse early embryo development. Our results showed that survivin mainly accumulated at chromosomes at metaphase stage and located at the spindle midzone at anaphase and telophase stages during the first cleavage. Loss of survivin activity led to the failure of cleavage in early mouse embryos. Further analysis indicated that survivin involved into spindle organization and chromosome alignment. Moreover, inhibition of survivin induced oxidative stress and DNA damage, showing with the increase of ROS level, the positive γH2A signal, and the increase of Rad51 level. We also observed the occurrence of autophagy and apoptosis in the survivin-inhibited embryos. In summary, our study suggested that survivin was a critical regulator for early embryo development through its regulation on spindle organization, chromosome alignment, and DNA damage.