HDAC6 inhibition disrupts maturational progression and meiotic apparatus assembly in mouse oocytes

HDAC6 抑制会破坏小鼠卵母细胞的成熟进程和减数分裂装置组装

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作者:Li Ling, Feifei Hu, Xiaoyan Ying, Juan Ge, Qiang Wang

Abstract

Histone deacetylases (HDACs) have been implicated in diverse biologic processes including transcriptional regulation, signal transduction, and developmental control. However, the role of HDAC6 in mammalian oocytes remains unknown. In the present study, by using Tubastatin A (TubA), a selective HDAC6 inhibitor, we 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 line with this observation, confocal microscopy revealed that kinetochore-microtubule attachment, a critical mechanism controlling chromosome movement, is compromised in TubA-treated oocytes markedly. Moreover, we noted that HDAC6 inhibition significantly increases the acetylation levels of α-tubulin in mouse oocytes, which may be associated with the defective phenotypes of TubA-treated oocytes by altering microtubule stability and dynamics. In sum, we discover a novel function of HDAC6 during oocyte maturation and suggest a potential pathway modulating meiotic apparatus assembly.

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