The Roles Of HDAC6 During Oocyte Maturation And Early Embryonic Development

Histone deacetylation is an important epigenetic modification associated with the repression of gene transcription,and its function is mainly exerted by the histone deacetylase(HDACs)family.Currently,HDACs have been reported to involve a variety of biological processes,including transcriptional regulation,signal transduction,and developmental control.However,the role of HDAC6 in mouse oocytes and early embryo development remains unknown.In the present study,by employing Tubastatin A(TubA),a highly selective HDAC6 inhibitor,we first examined the effects of HDAC6 on maturational progression and meiotic apparatus in mouse oocytes.We found that HDAC6 inhibition results in maturation arrest and disruption of spindle morphology and chromosome alignment in oocytes.Since kinetochore-microtubule(K-MT)attachments are the key mechanisms controlling chromosome movement,in line with our previous observation,we found that the K-MT attachments of oocytes in the TubA treated group are significantly impaired.In addition,we noticed that the decrease of HDAC6 enzyme activity significantly increased the acetylation of ?-tubulin in oocytes,suggesting that HDAC6 participates in the process of oocyte maturation by changing the stability and dynamic state of microtubules.Further,we examined the developmental progression of early embryos treated with TubA.Confocal microscopy revealed a disrupted incompact chromosome organization in the first mitosis of zygotes after TubA inhibition.Meanwhile,we observed that HDAC6 inhibition induced an increased level of reactive oxygen species(ROS)in the early embryos.In line with the notion that oxidative stress could lead to cell apoptosis,we detected high levels of H2 A.X phosphorylation at the 2-cell stage,where telomeres appeared focally enriched with ?H2A.X.To assess the blastocyst quality,cell apoptosis was evaluated by TUNEL assay.Significant positive signals were observed in the TubA-treated group compared to controls.Taken together,our data indicate that HDAC6 plays an important role in determing the quality of oocytes and embryos probably by modulating the acetylated status of histone and nonhistone proteins.