组蛋白去乙酰化酶1/2参与调控小鼠卵子发生的研究进展

The role of histone deacetylases 1/2 in regulating murine oogenesis

卵子发生是雌性哺乳动物的基本生殖过程,是后续受精及胚胎发育的基础。近年来研究表明,表观修饰在调控哺乳动物生殖过程(如卵子发生、精子发生、植入前胚胎发育及性别分化等)中扮演着重要的角色。以组蛋白乙酰化为例,组蛋白乙酰转移酶(histone acetyltransferases, HATs)和去乙酰化酶(histone deacetylases, HDACs)的动态变化参与调控生殖过程中众多关键生理事件发生时的基因激活与失活。其中,结构高度同源且功能冗余的HDAC1和HDAC2在卵子发生过程中扮演了关键的生理角色。HDAC1/2共同调控生长卵母细胞的整体转录水平以及凋亡水平,从而影响其后续发育,这体现了两者的功能冗余性。除此之外,HDAC1/2也能够不依赖于对方、独立地发挥作用。现有研究表明,HDAC2在卵子发生中更加重要,其可单独调控卵母细胞重新甲基化以及减数分裂染色体分离。HDAC1则在植入前胚胎发育过程中更为关键,单独缺乏HDAC1的胚胎干细胞增殖率降低,拟胚体体积减小且形状不规则。本综述拟就HDAC1/2在小鼠卵子发生中的调控作用及现有研究进展加以综述,为进一步认识表观修饰与生殖调控的关系提供参考。

Oogenesis is the basic reproductive process of female mammals and is essential for fertilization and embryo development.Recent studies have shown that epigenetic modifications play an important role in the regulation of mammalian reproductive processes(such as oogenesis, spermatogenesis, preimplantation embryo development and sex differentiation).Taking histone acetylation as an instance, the dynamic changes of histone acetyltransferases(HATs) and deacetylases(HDACs) are involved in the regulation of gene activation and inactivation when numerous key physiological events occur during reproduction.Thereinto, HDAC1 and HDAC2, which are highly homologous in terms of both structure and function, play a pivotal role in murine oogenesis.HDAC1 and 2 jointly regulate the global transcription and the incidence of apoptosis of growing oocytes and affect its subsequent growth and development, which reflects their compensatory function.In addition, HDAC1 and 2 also play a specific part in oogenesis respectively.It has shown that HDAC2 is more critical than HDAC1 for oocyte development, which regulates de novo DNA methylation and chromosome segregation.Reciprocally, HDAC1 is more critical than HDAC2 for preimplantation development.Deficiency of HDAC1 causes the decreased proliferation of embryonic stem cells and the smaller embryoid bodies with irregular shape.In this review, we summarized the role and the current research progress of HDAC1/2 in murine oogenesis, to provide a reference for further understanding the relationship between epigenetic modifications and reproductive regulation.