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Effects of mesenchymal stem cells on ovarian sirtuin 1 and caspase-3 in premature ovarian insufficiency mice

Yu-lan He^a,?, Yuan Yang^b,c,?, Ting Liao^a, Wei-wei Xie^a, Shi-huan Tang^a, Hong-mei Zhang^a, Lu Peng^a, Pei-ling Wu^a, Hui Zhang^a, Ting Long^d, Chun-bing Zheng^b,c,*, Xian-ping Zhang^a,*

 
ABSTRACT:     Human umbilical cord mesenchymal stem cells (HUCMSCs) can promote angiogenesis and reduce apoptosis, but their effects in premature ovarian insufficiency (POI) remain unclear. We found that HUCMSCs could improve ovarian function in POI mice through sirtuin 1 (SIRT1)/caspase-3. Female C57BL/6 mice (n = 45) were randomly divided into 3 groups: the POI and HUCMSC groups receiving cyclophosphamide for 14 days to induce POI and the control group receiving normal saline injections. HUCMSCs were injected into the tail veins of the mice in the HUCMSC group on days 14 and 28. We analyzed the mouse body and ovarian weight, ovarian structure, number of ovarian follicles, estrous cycles, serum hormone levels, ovarian SIRT1 and caspase-3 expression, and granulosa-cell apoptosis. The POI group showed decreased body weight, ovarian weight, number of follicles, and SIRT1 expression as well as impaired ovarian hormones, and increased caspase-3 and granulosa-cell apoptosis. Body weight, ovarian weight, disturbed estrous cycle, number of follicles, and hormone levels were improved after the HUCMSC intervention, while the ovarian SIRT1 level was increased, and caspase-3 and granulosa-cell apoptosis were decreased. HUCMSCs promote SIRT1 expression and downregulate caspase-3, thereby reducing ovarian granulosa-cell apoptosis and improving ovarian function in POI mice.

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* Corresponding author, E-mail: zunzhangxp@163.com, chbzhengm@126.com

Received 31 Jan 2024, Accepted 14 Aug 2024