α-酮戊二酸通过抑制细胞凋亡和上调糖酵解改善大鼠诱导性卵巢早衰。

Alpha-ketoglutarate ameliorates induced premature ovarian insufficiency in rats by inhibiting apoptosis and upregulating glycolysis.

作者信息

Li Tianlong, Liu Jie, Liu Ke, Wang Qian, Cao Junna, Xiao Ping, Yang Wenqin, Li Xiang, Li Jiangming, Li Meng, Tang Xuehan, Li Meixiang, Zhang Shun, Lei Xiaocan

机构信息

Institute of Clinical Anatomy and Reproductive Medicine, Department of Histology and Embryology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.

The First Affiliated Hospital of University of South China, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.

出版信息

Reprod Biomed Online. 2023 Apr;46(4):673-685. doi: 10.1016/j.rbmo.2023.01.005. Epub 2023 Jan 26.

DOI:10.1016/j.rbmo.2023.01.005

PMID:36894359

Abstract

RESEARCH QUESTION

What are the effects of alpha-ketoglutarate (α-KG) treatment on the ovarian morphology and ovarian reserve function of rats with cyclophosphamide (CTX)-induced premature ovarian insufficiency (POI)?

DESIGN

Thirty female Sprague Dawley rats were randomly allocated to a control group (n = 10) and a POI group (n = 20). Cyclophosphamide was administered for 2 weeks to induce POI. The POI group was then divided into two groups: a CTX-POI group (n = 10), administered normal saline, and a CTX-POI + α-KG group (n = 10), administered α-KG 250 mg/kg per day for 21 days. Body mass and fertility was assessed at the end of the study. Serum samples were collected for hormone concentration measurement, and biochemical, histopathological, TUNEL, immunohistochemical and glycolytic pathway analyses were conducted for each group.

RESULTS

The α-KG treatment increased body mass and ovarian index of rats, partially normalized their disrupted estrous cycles, prevented follicular loss, restored ovarian reserve, and increased pregnancy rate and litter sizes of rats with POI. It significantly reduced serum concentration of FSH (P < 0.001), increased that of oestradiol (P<0.001) and reduced apoptosis of granulosa cells (P = 0.0003). Moreover, α-KG increased concentrations of lactate (P = 0.015) and ATP (P = 0.025), reduced that of pyruvate (P<0.001) and increased expression of rate-limiting enzymes of glycolysis in the ovary.

CONCLUSIONS

α-KG treatment ameliorates the deleterious effects of CTX on the fertility of female rats, possibly by reducing the apoptosis of ovarian granulosa cells and restoring glycolysis.

摘要

研究问题

α-酮戊二酸（α-KG）治疗对环磷酰胺（CTX）诱导的大鼠卵巢早衰（POI）的卵巢形态和卵巢储备功能有何影响？

设计

将30只雌性Sprague Dawley大鼠随机分为对照组（n = 10）和POI组（n = 20）。给予环磷酰胺2周以诱导POI。然后将POI组分为两组：CTX-POI组（n = 10），给予生理盐水；CTX-POI + α-KG组（n = 10），每天给予250 mg/kg α-KG，共21天。在研究结束时评估体重和生育能力。收集血清样本测量激素浓度，并对每组进行生化、组织病理学、TUNEL、免疫组织化学和糖酵解途径分析。

结果

α-KG治疗增加了大鼠的体重和卵巢指数，部分恢复了紊乱的发情周期，防止了卵泡丢失，恢复了卵巢储备，并提高了POI大鼠的妊娠率和产仔数。它显著降低了血清促卵泡生成素浓度（P < 0.001），提高了雌二醇浓度（P < 0.001），并减少了颗粒细胞凋亡（P = 0.0003）。此外，α-KG增加了乳酸浓度（P = 0.015）和ATP浓度（P = 0.025），降低了丙酮酸浓度（P < 0.001），并增加了卵巢中糖酵解限速酶的表达。