Enhanced glycolysis in granulosa cells promotes the activation of primordial follicles through mTOR signaling.
Enhanced glycolysis in granulosa cells promotes the activation of primordial follicles through mTOR signaling.
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颗粒细胞中增强的糖酵解通过 mTOR 信号传导促进原始卵泡的激活
DOI：
10.1038/s41419-022-04541-1
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发表时间：
2022-01-27
影响因子：
9
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Zhang X;Zhang W;Wang Z;Zheng N;Yuan F;Li B;Li X;Deng L;Lin M;Chen X;Zhang M
在哺乳动物中，不可再生的原始卵泡以有序的方式被激活，以维持生殖生命的寿命。前颗粒细胞中的哺乳动物雷帕霉素靶蛋白（mTOR）-KIT配体（KITL）信号传导和卵母细胞中的磷脂酰肌醇3-激酶（PI 3 K）-蛋白激酶B（Akt）-叉头盒O3 a（FOXO 3a）信号传导对于原始卵泡激活是重要的。激活过程伴随着能量代谢的增强，但因果关系尚不清楚。在本研究中，在小鼠原基卵泡向初级卵泡转化过程中，颗粒细胞中糖酵解相关蛋白GLUT 4，HK 1，PFKL与PKM 2得水平显著升高，而卵母细胞中得水平则降低.体外短期丙酮酸剥夺和体内急性禁食均增加小鼠卵巢中糖酵解相关基因和蛋白水平，降低AMPK活性，增加mTOR活性。下游通路Akt和FOXO 3a被磷酸化，导致小鼠原始卵泡激活。2-脱氧葡萄糖（2-DG）阻断糖酵解，但KIT抑制剂ISCK 03不阻断前颗粒细胞和卵母细胞之间的通讯网络，降低了短期丙酮酸剥夺促进的mTOR活性。在原始卵泡向初级卵泡转变过程中，人类颗粒细胞中糖酵解也增加，短期丙酮酸剥夺通过增加卵巢组织中糖酵解相关蛋白水平与mTOR活性，促进了人类原始卵泡得激活.总之，颗粒细胞中糖酵解的增强通过mTOR信号传导促进原始卵泡的激活。这些发现为糖酵解障碍和POI/PCOS之间的关系提供了新的见解。
In mammals, nonrenewable primordial follicles are activated in an orderly manner to maintain the longevity of reproductive life. Mammalian target of rapamycin (mTOR)-KIT ligand (KITL) signaling in pre-granulosa cells and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-forkhead Box O3a (FOXO3a) signaling in oocytes are important for primordial follicle activation. The activation process is accompanied by the enhancement of energy metabolism, but the causal relationship is unclear. In the present study, the levels of glycolysis-related proteins GLUT4, HK1, PFKL, and PKM2 were significantly increased in granulosa cells but were decreased in oocytes during the mouse primordial-to-primary follicle transition. Both short-term pyruvate deprivation in vitro and acute fasting in vivo increased the glycolysis-related gene and protein levels, decreased AMPK activity, and increased mTOR activity in mouse ovaries. The downstream pathways Akt and FOXO3a were phosphorylated, resulting in mouse primordial follicle activation. The blockade of glycolysis by 2-deoxyglucose (2-DG), but not the blockade of the communication network between pre-granulosa cells and oocyte by KIT inhibitor ISCK03, decreased short-term pyruvate deprivation-promoted mTOR activity. Glycolysis was also increased in human granulosa cells during the primordial-to-primary follicle transition, and short-term pyruvate deprivation promoted the activation of human primordial follicles by increasing the glycolysis-related protein levels and mTOR activity in ovarian tissues. Taken together, the enhanced glycolysis in granulosa cells promotes the activation of primordial follicles through mTOR signaling. These findings provide new insight into the relationship between glycolytic disorders and POI/PCOS.
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影响因子：
5.9
作者：
Laufenberg LJ;Crowell KT;Lang CH
通讯作者：
Lang CH
ESR1、HK3 和 BRSK1 基因变异与自然绝经年龄和卵巢早衰有关
影响因子：
3.7
作者：
Qin Y;Sun M;You L;Wei D;Sun J;Liang X;Zhang B;Jiang H;Xu J;Chen ZJ
通讯作者：
Chen ZJ
影响因子：
2.2
作者：
Morales-Martínez FA;Sordia-Hernández LH;Ruiz MM;Garcia-Luna S;Valdés-Martínez OH;Vidal-Gutierez O
通讯作者：
Vidal-Gutierez O
影响因子：
56.9
作者：
Reddy, Pradeep;Liu, Lian;Liu, Kui
通讯作者：
Liu, Kui
DOI：
10.1093/humrep/det388
发表时间：
2014-01
期刊：
Human reproduction (Oxford, England)
影响因子：
--
作者：
Anderson RA;McLaughlin M;Wallace WH;Albertini DF;Telfer EE
通讯作者：
Telfer EE