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HDAC3 抑制破坏猪卵母细胞成熟过程中减数分裂装置的组装。

HDAC3 inhibition disrupts the assembly of meiotic apparatus during porcine oocyte maturation.

机构信息

College of Animal Science & Technology, Nanjing Agricultural University, Nanjing, China.

出版信息

J Cell Physiol. 2019 Jul;234(7):10178-10183. doi: 10.1002/jcp.27687. Epub 2018 Oct 30.

DOI:10.1002/jcp.27687
PMID:30378138
Abstract

Histone deacetylases (HDACs) are involved in a wide array of biological processes. However, the role of HDAC3 in porcine oocytes remains unclear. In the current study, we examine the effects of HDAC3 inhibition on porcine oocyte maturation using RGFP966, a selective HDAC3 inhibitor. We find that suppression of HDAC3 activity prevents not only the expansion of cumulus cells but also the meiotic progression of oocytes. It is interesting to note that HDAC3 displays a spindle-like distribution pattern as the porcine oocytes enter meiosis. In line with this, confocal microscopy reveals the high frequency of spindle defects and chromosomal congression failure in metaphase oocytes exposed to RGFP966. Moreover, HDAC3 inhibition results in the hyperacetylation of α-tubulin during oocyte meiosis. These findings indicate that HDAC3 activity might control the microtubule stability via the deacetylation of tubulin, which is critical for maintaining the proper spindle assembly, accurate chromosome separation, and orderly meiotic progression during porcine oocyte maturation.

摘要

组蛋白去乙酰化酶(HDACs)参与了广泛的生物学过程。然而,HDAC3 在猪卵母细胞中的作用尚不清楚。在本研究中,我们使用选择性 HDAC3 抑制剂 RGFP966 研究了 HDAC3 抑制对猪卵母细胞成熟的影响。我们发现,抑制 HDAC3 的活性不仅阻止了卵丘细胞的扩展,还阻止了卵母细胞的减数分裂进程。有趣的是,HDAC3 在猪卵母细胞进入减数分裂时呈现出类似于纺锤体的分布模式。与此一致的是,共聚焦显微镜显示,在 RGFP966 处理的中期卵母细胞中,纺锤体缺陷和染色体向心性聚集失败的频率很高。此外,HDAC3 抑制导致卵母细胞减数分裂过程中微管蛋白α- tubulin 的过度乙酰化。这些发现表明,HDAC3 的活性可能通过去乙酰化微管蛋白来控制微管的稳定性,这对于维持适当的纺锤体组装、准确的染色体分离和有序的减数分裂进程至关重要。

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