颗粒状细胞中HAT1表达的降低在老鼠卵巢衰老过程中扰乱了卵细胞半转化
Bichun Guo1,2, Sainan Zhang3, Shanshan Wang1
1Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Reproductive biology and endocrinology : RB&E
|November 1, 2023
概括
卵巢颗粒细胞中希斯乙转移酶1 (HAT1) 的表达减少有助于与年龄相关的卵细胞无化. 抑制HAT1会影响卵细胞成熟,这表明HAT1是改善生育能力的治疗点.
科学领域:
- 生殖生物学 生殖生物学
- 分子遗传学 分子遗传学
- 细胞衰老 细胞衰老
背景情况:
- 先进的孕产妇年龄与卵细胞无体积的增加和卵子质量的降低有关.
- 在老化的卵细胞中,积体底层的分子机制尚不清楚.
- 基因组乙转移酶1 (HAT1) 对发育和基因组稳定性至关重要,并与器官衰老有关.
研究的目的:
- 研究HAT1在卵巢衰老和卵细胞成熟中的作用.
- 阐明HAT1影响老年女性卵细胞质量的分子机制.
主要方法:
- 免疫组织化学和免疫血栓检测,以评估老鼠卵巢中的HAT1水平.
- 在体外培养的积卵细胞复合物 (COCs) 与酸 (AA) 或siRNA抑制HAT1.
- 介质性参数的统计分析,动脉化和胚胎形成率.
- 使用类似于人体颗粒素的KGN细胞进行机制研究.
主要成果:
- 在年轻小鼠卵巢颗粒细胞 (GCs) 中,HAT1的表达高,在老年GCs中显著下降.
- 在GC中抑制HAT1导致极体挤出 (PBE) 减少,卵细胞中中介性缺陷和动质积分增加.
- HAT1乙化叉头盒转录因子O1 (FoxO1),促进其核转位.
- 乙化FoxO1的核转位可提高GC中的安菲瑞古林 (AREG) 表达的调节,这对卵细胞中离子变异至关重要.
结论:
- 在GC中减少HAT1表达是导致卵细胞中与年龄相关的介质缺陷的潜在原因.
- 在卵巢衰老期间,HAT1在维持卵细胞介质完整性方面发挥着关键作用.
- 向HAT1提供了一种潜在的治疗策略,以减少无卵性卵子细胞和改善老年妇女的生育能力.
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