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

• Published in: Reproductive biomedicine online 2023-04, Vol.46 (4), p.673-685
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: alpha-ketoglutarate; Animals; Apoptosis; Cyclophosphamide - adverse effects; Female; granulosa cell; Humans; Ketoglutaric Acids - adverse effects; Menopause, Premature; ovarian reserve; Pregnancy; premature ovarian insufficiency; Primary Ovarian Insufficiency - therapy; Rats; Rats, Sprague-Dawley
• ISSN: 1472-6483; 1472-6491
• DOI: 10.1016/j.rbmo.2023.01.005

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)? 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. 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