HDAC6 inhibition induces the failure of mouse early embryonic development.

Abstract

Histone deacetylases (HDACs) have been implicated in numerous biological events. However, to date, the role of HDAC6 in early embryos remains unknown. In the current study, Tubastatin A (TubA), a potent HDAC6 inhibitor, was used to block HDAC6 activity in mouse embryos. We found that TubA exposure significantly reduced the blastocyst formation of early embryos. Confocal microscopy revealed the markedly increased chromosomal congression failure in the mouse embryos treated with the HDAC6 inhibitor. Moreover, the HDAC6 inhibition resulted in the overproduction of reactive oxygen species (ROS) in embryos. In addition, we observed the accumulation of phosphorylated γH2AX in TubA-treated embryos, indicative of the increased DNA damage. In line with this, cell apoptosis of blastocysts was frequently detected in HDAC6-deficient embryos compared with their controls. Altogether, our data indicate that HDAC6 may serve as an important regulator of chromatin structure and mitochondrial function, determining the developmental potential of theearly embryos of mouse.