Inhibition of HDAC4 in granulosa cells improves co-cultured porcine oocyte maturation in vitro independently of LH.

IF 3.7 2区 生物学 Q1 DEVELOPMENTAL BIOLOGY
Development Pub Date : 2025-04-01 Epub Date: 2025-04-08 DOI:10.1242/dev.204618
Zhenzi Zuo, Yibing Bao, Lin Lin, Hengxing Li, Tengteng Wang, Guoliang Xia, Chao Wang
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引用次数: 0

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.

抑制猪颗粒细胞中HDAC4可促进体外不依赖LH的共培养卵母细胞成熟。
在家畜中,黄体生成素(LH)激增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(hdac)在调节配子发生中的关键作用,本研究探讨了猪卵泡颗粒细胞(GCs)中hdac在卵母细胞成熟过程中介导LH作用的作用。结果显示,在促卵泡激素(FSH)刺激下,培养GCs中组蛋白去乙酰化酶4 (HDAC4)水平呈时间依赖性升高,而在LH治疗下,HDAC4水平显著降低。lh诱导的HDAC4的减少是通过细胞外信号调节激酶1/2 (ERK1/2)的积累介导的,ERK1/2随后增加H3K18乙酰化,并促进SMAD家族成员3 (SMAD3)募集到egf样生长因子双调节蛋白(Areg)的启动子。值得注意的是,特异性抑制HDAC4在体外独立于LH促进卵母细胞成熟,并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。综上所述,卵泡体细胞中的HDAC4作为促性腺激素应答的表观遗传修饰因子,负向调控猪卵母细胞减数分裂的恢复。
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来源期刊
Development
Development 生物-发育生物学
CiteScore
6.70
自引率
4.30%
发文量
433
审稿时长
3 months
期刊介绍: Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community. Development includes a Techniques and Resources section for the publication of new methods, datasets, and other types of resources. Papers describing new techniques should include a proof-of-principle demonstration that the technique is valuable to the developmental biology community; they need not include in-depth follow-up analysis. The technique must be described in sufficient detail to be easily replicated by other investigators. Development will also consider protocol-type papers of exceptional interest to the community. We welcome submission of Resource papers, for example those reporting new databases, systems-level datasets, or genetic resources of major value to the developmental biology community. For all papers, the data or resource described must be made available to the community with minimal restrictions upon publication. To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.
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