ABSTRACT
In domestic animals, the mechanisms by which the luteinizing hormone (LH) surge induces oocyte meiosis resumption and maturation through follicular somatic cells remain unclear. Given the pivotal roles of histone deacetylases in regulating gametogenesis, this study investigated the roles of histone deacetylases in follicular granulosa cells in mediating LH action during oocyte maturation in pigs. The results showed that histone deacetylase 4 (HDAC4) levels in cultured granulosa cells increased in a time-dependent manner with follicle-stimulating hormone stimulation but significantly decreased with LH treatment. The LH-induced reduction of HDAC4 was mediated by the accumulation of extracellular signal-regulated kinase 1/2 (ERK1/2), which subsequently increased H3K18 acetylation and promoted the recruitment of SMAD family member 3 (SMAD3) to the promoter of the EGF-like growth factor amphiregulin (AREG). Notably, specific inhibition of HDAC4 promoted oocyte maturation independently of LH in vitro, and the developmental potential of these matured oocytes was comparable to those induced by LH in vitro. In conclusion, HDAC4 in follicular somatic cells serves as a gonadotrophin-responsive epigenetic modification factor that negatively regulates oocyte meiosis resumption in pigs.
Footnotes
Author contributions
Conceptualization: Z.Z.; Data curation: Z.Z.; Formal analysis: Z.Z., Y.B.; Funding acquisition: C.W.; Methodology: Z.Z.; Project administration: Z.Z., C.W.; Supervision: G.X., C.W.; Validation: Z.Z., Y.B.; Visualization: Z.Z., Y.B.; Writing – original draft: Z.Z.; Writing – review & editing: Z.Z., L.L., H.L., T.W., C.W.
Funding
This work was supported by the National Key Research and Development Program of China (2023YFD1300501, 2022YFC2703803, 2018YFC1003700 and 2018YFC1003801), the National Natural Science Foundation of China (32371167, 32071132, 32270904 and 32070839), the 2115 Talent Development Program of China Agricultural University.
Data availability
All relevant data can be found within the article and its supplementary information.
