Aurora B prevents aneuploidy via MAD2 during the first mitotic cleavage in oxidatively damaged embryos

A high rate of chromosome aneuploidy is exhibited in in vitro fertilization (IVF)-derived embryos. Our previous experiments suggested that reactive oxygen species (ROS) can activate Mad2, a key protein in the spindle assembly checkpoint (SAC), and delay the first mitotic, providing time to prevent the formation of embryonic aneuploidy. We aimed to determine whether mitotic kinase Aurora B was involved in the SAC function to prevent aneuploidy in IVF-derived embryos.

We analysed aneuploidy formation and repair during embryo pre-implantation via 4',6-diamidino-2-phenylindole (DAPI) staining and karyotype analysis. We assessed Aurora B activation by immunofluorescence and investigated the effect of Aurora B inhibition on embryo injury-related variables, such as embryonic development, ROS levels, mitochondrial membrane potential and γH2AX-positive expression.

We observed the expression and phosphorylation of Thr232 in Aurora B in oxidative stress-induced zygotes. Moreover, inhibition of Aurora B caused chromosome mis-segregation, abnormal spindle structures, abnormal chromosome number and reduced expression of Mad2 in IVF embryos. Our results suggest that Aurora B causes mitotic arrest and participates in SAC via Mad2 and H3S10P, which is required for self-correction of aneuploidies.

We demonstrate here that oxidative stress-induced DNA damage triggers Aurora B-mediated activation of SAC, which prevents aneuploidy at the first mitotic cleavage in early mouse IVF embryos.