Zuo Zhenzi, Bao Yibing, Lin Lin, Li Hengxing, Wang Tengteng, Xia Guoliang, Wang Chao
State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
State Key Laboratory of Cancer Biology and Department of Physiology and Pathophysiology, Fourth Military Medical University, Xi'an, 710032China.
Development. 2025 Apr 1;152(7). doi: 10.1242/dev.204618. Epub 2025 Apr 8.
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.
在家畜中，促黄体生成素（LH）峰通过卵泡体细胞诱导卵母细胞减数分裂恢复和成熟的机制尚不清楚。鉴于组蛋白去乙酰化酶在调节配子发生中的关键作用，本研究调查了组蛋白去乙酰化酶在猪卵母细胞成熟过程中介导LH作用的卵泡颗粒细胞中的作用。结果表明，培养的颗粒细胞中组蛋白去乙酰化酶4（HDAC4）水平随卵泡刺激素刺激呈时间依赖性增加，但随LH处理显著降低。LH诱导的HDAC4减少由细胞外信号调节激酶1/2（ERK1/2）的积累介导，ERK1/2随后增加H3K18乙酰化并促进SMAD家族成员3（SMAD3）募集到表皮生长因子样生长因子双调蛋白（AREG）的启动子上。值得注意的是，特异性抑制HDAC4在体外可独立于LH促进卵母细胞成熟，且这些成熟卵母细胞的发育潜力与LH在体外诱导的卵母细胞相当。总之，卵泡体细胞中的HDAC4作为一种促性腺激素反应性表观遗传修饰因子，对猪卵母细胞减数分裂恢复起负调节作用。
