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低毒性介质干细胞衍生异体细胞循环Dennd2a通过与LDHA相互作用来调节颗粒细胞糖解

Wenxin Li^1,2, Minjun Lu^1,2, Junyu Shang^1,2

¹Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University, No. 20 Zhengdong Road, Zhenjiang, Jiangsu Province, 212001, China.

Stem cell research & therapy

|December 19, 2024

概括

低氧诱导的外生体增强卵巢糖解和粒粉细胞功能,为过早卵巢缺陷 (POI) 提供潜在的治疗方法. 这种治疗通过改善卵巢功能和减少细胞死亡来恢复POI大鼠的生育能力.

科学领域:

生殖生物学和内分泌学.
细胞代谢和信号传递
通过外体介导的细胞间通信.

背景情况:

过早卵巢衰竭 (POI) 是一种影响女性生育能力的疾病,其特点是卵巢功能障碍.
卵巢颗粒细胞 (GCs) 对于卵细胞发育至关重要,并依赖糖解来获得能量.
缺氧诱导的外体环RNAs在POI病原和糖解中的作用在很大程度上是未知的.

研究的目的:

在POI的老鼠模型中研究缺氧诱导的外体环RNAs的生物功能和分子机制.
探索介质干细胞衍生异构体 (HM-Exs) 的治疗潜力,以恢复POI的卵巢功能和生育能力.
在POI的背景下阐明circDennd2a在调节GC糖解和亡中的特定作用.

主要方法:

通过使用循环胺的管理,建立了POI的老鼠模型.
对POI大鼠进行了PBS,诺莫克西亚诱导的外体细胞 (NM-Exs) 或缺氧诱导的外体细胞 (HM-Exs) 的治疗.
卵巢功能,生育能力,能量代谢物,GC细胞亡,增殖和circDennd2a表达被评估使用各种测试 (qRT-PCR,西部斑点,CCK-8,EDU,TUNEL,ECAR,ATP,乳酸盐,Pyruvate).

主要成果:

POI与卵巢糖解降低和血清和GCs中的circDennd2a耗尽有关.
HM-Exs治疗显著增强了卵巢糖解,减少了GC细胞亡,促进了繁殖,改善了雌性周期和性激素水平.
来自HM-Exs的circDennd2a与乳酸脱酶A (LDHA) 相互作用,增加了它的酶活性,并维持了GC的糖解功能.

结论:

源自HM-Exs的cirDennd2a促进了LDHA活性,并增强了GC的糖分分解能力,在缓解POI方面发挥了至关重要的作用.
通过HM-Exs提供的CircDennd2a显示了恢复POI生育能力的显著治疗潜力.
HM-Exs-circDennd2a代表了早期卵巢衰竭的有前途的临床诊断和治疗标.

关键词:

圆圈nd2a2a2a2a2a 圆圈nd2a2a2a 圆圈nd2a2a 圆圈nd2a 外基因组是外基因组的组成部分.葡萄糖溶解是什么? 葡萄糖溶解氧气过低是因为缺氧.过早的卵巢功能不全 (POI)

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