RGFP966 Exhibits an LH-Like Efficacy in Promoting Tan Sheep Oocyte Maturation and Subsequent Developmental Competence

IF 3.7 2区农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE

Journal of animal science Pub Date : 2026-10-05 DOI:10.1093/jas/skag321

Xiangyan Wang,Pengfei Li,Donghuan Lv,Yan Zhang,Zhipeng Qi,Jiaqi Shi,Young Tang,Qiang Chen,Xinfeng Liu

{"title":"RGFP966 Exhibits an LH-Like Efficacy in Promoting Tan Sheep Oocyte Maturation and Subsequent Developmental Competence","authors":"Xiangyan Wang,Pengfei Li,Donghuan Lv,Yan Zhang,Zhipeng Qi,Jiaqi Shi,Young Tang,Qiang Chen,Xinfeng Liu","doi":"10.1093/jas/skag321","DOIUrl":null,"url":null,"abstract":"Abstract RGFP966 is a selective inhibitor of histone deacetylase 3 (HDAC3). This study aimed to evaluate whether HDAC3 inhibition could promote in vitro maturation (IVM) and subsequent embryo development in Tan sheep oocytes, and to compare its efficacy with luteinizing hormone (LH). Immunofluorescence analysis revealed that HDAC3 expression was significantly decreased in metaphase II (MII) oocytes compared to the germinal vesicle (GV) stage (P &lt; 0.001). Western blotting verified that RGFP966 suppressed HDAC3 deacetylase activity in Tan sheep granulosa cells, increasing the acetylation of downstream substrates H3K9ac, H3K14ac and H4K5ac (P &lt; 0.01). Treatment with RGFP966 significantly promoted polar body 1 (PB1) extrusion, achieving a maturation rate comparable to the LH-treated group. Mechanistically, RGFP966 treatment significantly enhanced mitochondrial distribution (P &lt; 0.01), upregulated GPX4 expression (P &lt; 0.001), and accordingly reduced intracellular reactive oxygen species (ROS) levels (P &lt; 0.001). Moreover, RGFP966 significantly decreased the rate of spindle/chromosome misalignment (P &lt; 0.001) and reduced early apoptosis (indicated by reduced Annexin-V staining) in MII oocytes (P &lt; 0.001), without inducing additional DNA double strand breaks, as evidenced by unchanged γH2AX levels. Subsequent in vitro fertilization (IVF) demonstrated that the 2-cell cleavage and blastocyst rates of oocytes matured with RGFP966 were comparable to those of the LH group, and the resultant blastocysts exhibited normal expression patterns of lineage markers (CDX2 and SOX2). In conclusion, HDAC3 inhibitor RGFP966 promotes Tan sheep oocyte IVM and subsequent developmental competence with an efficacy equivalent to LH. This process relies on alleviating oxidative stress by enhancing mitochondrial distribution and GPX4 expression, while preserving genomic stability during meiosis. These findings provide a theoretical basis for the potential application of HDAC3 inhibitors as effective additives in ovine IVM systems.","PeriodicalId":14895,"journal":{"name":"Journal of animal science","volume":"42 1","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of animal science","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1093/jas/skag321","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"AGRICULTURE, DAIRY & ANIMAL SCIENCE","Score":null,"Total":0}

引用次数: 0

Abstract

Abstract RGFP966 is a selective inhibitor of histone deacetylase 3 (HDAC3). This study aimed to evaluate whether HDAC3 inhibition could promote in vitro maturation (IVM) and subsequent embryo development in Tan sheep oocytes, and to compare its efficacy with luteinizing hormone (LH). Immunofluorescence analysis revealed that HDAC3 expression was significantly decreased in metaphase II (MII) oocytes compared to the germinal vesicle (GV) stage (P < 0.001). Western blotting verified that RGFP966 suppressed HDAC3 deacetylase activity in Tan sheep granulosa cells, increasing the acetylation of downstream substrates H3K9ac, H3K14ac and H4K5ac (P < 0.01). Treatment with RGFP966 significantly promoted polar body 1 (PB1) extrusion, achieving a maturation rate comparable to the LH-treated group. Mechanistically, RGFP966 treatment significantly enhanced mitochondrial distribution (P < 0.01), upregulated GPX4 expression (P < 0.001), and accordingly reduced intracellular reactive oxygen species (ROS) levels (P < 0.001). Moreover, RGFP966 significantly decreased the rate of spindle/chromosome misalignment (P < 0.001) and reduced early apoptosis (indicated by reduced Annexin-V staining) in MII oocytes (P < 0.001), without inducing additional DNA double strand breaks, as evidenced by unchanged γH2AX levels. Subsequent in vitro fertilization (IVF) demonstrated that the 2-cell cleavage and blastocyst rates of oocytes matured with RGFP966 were comparable to those of the LH group, and the resultant blastocysts exhibited normal expression patterns of lineage markers (CDX2 and SOX2). In conclusion, HDAC3 inhibitor RGFP966 promotes Tan sheep oocyte IVM and subsequent developmental competence with an efficacy equivalent to LH. This process relies on alleviating oxidative stress by enhancing mitochondrial distribution and GPX4 expression, while preserving genomic stability during meiosis. These findings provide a theoretical basis for the potential application of HDAC3 inhibitors as effective additives in ovine IVM systems.

查看原文本刊更多论文

RGFP966在促进滩羊卵母细胞成熟和随后的发育能力方面表现出类似lh的功效

RGFP966是一种选择性组蛋白去乙酰化酶3 （HDAC3）抑制剂。本研究旨在评价抑制HDAC3是否能促进滩羊卵母细胞体外成熟（IVM）和随后的胚胎发育，并比较其与黄体生成素（LH）的作用。免疫荧光分析显示，与生发囊泡（GV）期相比，HDAC3在中期（MII）卵母细胞中的表达显著降低（P <； 0.001）。Western blotting证实RGFP966抑制了滩羊颗粒细胞中HDAC3去乙酰化酶的活性，增加了下游底物H3K9ac、H3K14ac和H4K5ac的乙酰化（P <； 0.01）。RGFP966处理显著促进了极体1 （PB1）的挤压，达到与lh处理组相当的成熟率。在机制上，RGFP966处理显著增强了线粒体分布（P <； 0.01），上调了GPX4表达（P <； 0.001），并相应地降低了细胞内活性氧（ROS）水平（P <； 0.001）。此外，RGFP966显著降低了MII卵母细胞的纺锤体/染色体错配率（P <； 0.001），减少了早期凋亡（通过减少Annexin-V染色表明）（P <； 0.001），而没有引起额外的DNA双链断裂，这一点可以通过γH2AX水平不变来证明。随后的体外受精（IVF）表明，RGFP966成熟的卵母细胞的2细胞分裂率和囊胚率与LH组相当，所得到的囊胚具有正常的谱系标记（CDX2和SOX2）表达模式。综上所述，HDAC3抑制剂RGFP966对滩羊卵母细胞IVM和随后的发育能力的促进作用与LH相当。这一过程依赖于通过增强线粒体分布和GPX4表达来减轻氧化应激，同时在减数分裂期间保持基因组的稳定性。这些发现为HDAC3抑制剂作为有效添加剂在绵羊IVM系统中的潜在应用提供了理论基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of animal science 农林科学-奶制品与动物科学

CiteScore

4.80

自引率

12.10%

发文量

1589

审稿时长

3 months

期刊介绍： The Journal of Animal Science (JAS) is the premier journal for animal science and serves as the leading source of new knowledge and perspective in this area. JAS publishes more than 500 fully reviewed research articles, invited reviews, technical notes, and letters to the editor each year. Articles published in JAS encompass a broad range of research topics in animal production and fundamental aspects of genetics, nutrition, physiology, and preparation and utilization of animal products. Articles typically report research with beef cattle, companion animals, goats, horses, pigs, and sheep; however, studies involving other farm animals, aquatic and wildlife species, and laboratory animal species that address fundamental questions related to livestock and companion animal biology will be considered for publication.