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Mechanism of human umbilical cord mesenchymal stem cells for improving the ovarian function of mice injured by 4-vinylcyclohexene diepoxide |
1.National Research Institute for Family Planning, Beijing, 100081; 2. Graduate School, Peking Union Medical College, Beijing; 3. Weifang Maternal and Child Health Care Hospital, Shandong Province |
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Abstract To establish the mouse model with primary ovarian insufficiency (POI) using 4-vinylcyclohexene diepoxide (VCD), and to explore the mechanism of action of human umbilical cord mesenchymal stem cells (HUMSCs) for improving the ovarian function of the mice. Methods: 30 female ICR mice with 14 days of normal estrous cycle were randomly divided into control group, group A, and group B (10 mice in each group). The model mice in group A and group B were established by injection of VCD (160 mg/kg) for 20 days, and the mice in the control group were given intraperitoneal equal amount of sesame oil for 20 days. The mice in group B were given HUMSCs (106 cells/ml) injection with 0.2ml/mouse/day for two days, and the mice in group A were given equal amount of saline injection. The number of follicles at all levels, the number of atretic follicles, the levels of serum estradiol (E2), follicle stimulating hormone (FSH), and anti-mullerian hormone (AMH), the levels of iron, malondialdehyde(MDA), and GSH in ovarian tissue, and the protein expression levels of SCL7A11, GPX4, ACSL4, and DMT1 in ovarian tissue of the mice were detected on D 21. Results: Compared with those of the mice in group A, the body weight of the mice in group B was significantly higher, the duration of estrous cycle was significantly shorter, the ovarian morphology had improved significantly, the number of follicles was significantly higher, the number of atretic follicles was significantly lower, the serum E2 and FSH levels were significantly higher, the AMH level was significantly lower, the levels of iron and MDA in ovarian tissue were significantly lower, the GSH level in ovarian tissue was significantly higher, the expression levels of SCL7A11, GPX4, and DMT1 proteins in ovarian tissues were significantly higher, and the expression level of ACSL4 protein in ovarian tissues were significantly lower (all P<0.05). Conclusion: HUMSCs can improve the ovarian function of the mice with POI induced by VCD through inhibiting iron death in the ovary of these mice.
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