HDAC11 in ovarian granulosa cells coordinates LH in the maturation of oocytes in Tan sheep

Oocyte maturation plays an important role in supporting mammalian reproduction. Histone deacetylase 11 (HDAC11), the only member of the class IV histone deacetylase family and the smallest histone deacetylases (HDACs), has been shown to regulate oocyte maturation in mice and pigs. However, the epigenetic effects of HDACs in follicular granulosa cells in response to LH induction remain elusive in sheep. In this study, the effects of follicular somatic cell-derived HDAC11 on oocyte maturation in Tan sheep are evaluated. The expression changes of HDAC11 and related proteins are detected by means of immunofluorescence, immunohistochemistry, western blot analysis and enzyme-linked immunosorbent assay. Our results indicate that the level of HDAC11 in follicular granulosa cells as well as oocytes in Tan sheep increases with the growth and maturation of the follicles. Specific inhibition of HDAC11 by SIS17 remarkably reduces the oocyte maturation rate under LH supplementation in vitro. Accordingly, the acetylation level of H3K9 in granulosa cells is increased, while the EGF-like growth factor AREG is remarkably decreased. Furthermore, inhibition of HDAC11 markedly decreases the level of YAP1, which is a negative regulator of AREG in granulosa cells. Conclusively, HDAC11 in the granulosa cells of Tan sheep contributes to the LH induced production of AREG during oocyte in vitro maturation by decreasing the level of H3K9 acetylation and increasing the level of YAP1.