HDAC1 in the Ovarian Granulosa Cells of Tan Sheep Improves Cumulus Cell Expansion and Oocyte Maturation Independently of the EGF-like Growth Factors

SIMPLE SUMMARY: This study aimed to explore the possible role of histone deacetylase 1 (HDAC1), an epigenetic modifying enzyme, in the improvement of oocyte maturation recovered from the Tan sheep of China. We supplemented a specific inhibitor of HDAC1 to in vitro-cultured cumulus oocyte complexes (COCs). The results showed that the cumulus cell expansion and oocyte maturation ratio were impaired, while the production of the epidermal growth factor (EGF) was only slightly changed, despite the fact that the pan-acetylation levels of the histones were significantly elevated. This study implies that HDAC1 may participate in the maturation of oocytes in Tan sheep independently of the classic gonadotrophin-induction pathway. ABSTRACT: Previous studies have shown that some of the histone deacetylases (HDACs) play diverse roles in the regulation of ovarian somatic cell development, oocyte maturation and early embryonic development in different species including sheep. This study aimed to clarify whether HDAC1 also played pivotal roles in regulating oocyte maturation in Tan sheep. The results showed that HDAC1 was expressed in the nuclei of both the granulosa cells and oocytes of the growing follicles in the Tan sheep’s ovaries. However, the level of HDAC1 was unaffected by luteinizing hormone (LH) induction in cultured granulosa cells. Meanwhile, the specific inhibition of HDAC1 using pyroxamide did not induce significant changes in the expression levels of EGF-like growth factors in vitro, whereas both the cumulus expansion and oocyte maturation of the cultured cumulus oocyte complexes (COCs) were significantly inhibited by pyroxamide. Additionally, the numbers of histone acetylation sites (H4K5, H4K12, H3K14 and H3K9) in ovarian granulosa cells were significantly increased. In conclusion, a constant expression of HDAC1 in the growing follicles of Tan sheep may be pivotal for supporting oocyte growth and maturation, although its action may not be closely correlated with LH induction, nor does it directly affect the expression of the EGF-like factors. Our study implies that there may exist diverse functions of the respective HDACs in modulating female reproduction in sheep.