CHK1-CENP B/MAD2 is associated with mild oxidative damage-induced sex chromosome aneuploidy of male mouse embryos during in vitro fertilization.

CHK1-CENP B/MAD2 is associated with mild oxidative damage-induced sex chromosome aneuploidy of male mouse embryos during in vitro fertilization. Free Radic Biol Med. 2019 Apr 28;: Authors: Huang Y, Ha S, Li Z, Li J, Xiao W Abstract A high incidence of aneuploidy is observed in in vitro fertilization (IVF)-derived embryos, but the formation and repair mechanisms are unknown. Here, we investigated the effects of slightly increased reactive oxygen species (ROS) produced by in vitro culture conditions on embryo aneuploidy and the roles of the spindle assembly checkpoint (SAC) protein, mitotic arrest-deficient 2 (MAD2), and the DNA damage response (DDR) protein, checkpoint kinase 1 (CHK1), in aneuploidy repair. By assessing chromosome abnormalities via DAPI staining, karyotype analysis and next-generation sequencing technology, we demonstrated that mild oxidative damage mainly increased the risk of sex chromosome aneuploidy in male mouse embryos (41,XXY,+X and 41,XYY,+Y) through chromosome mis-segregation during the first mitosis. Isobaric tags for relative and absolute quantitation technology revealed that mild oxidative damage inhibited the expression of male reproduction-related proteins, including a kinase anchor protein 4 (AKAP4), whose gene is located on mouse/human Chromosome X. Under mild oxidative damage, abrogation of MAD2 by MAD2 inhibitor-1 (M2I-1) or CHK1 by siRNA microinjection increased sex chromosome mosaicism rate and red...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research