Effect of adipose-derived mesenchymal stem cell transplantation on cyclophosphamide-induced ovarian damage in rats / 中南大学学报(医学版)

ABSTRACT

To explore the effect of adipose-derived mesenchymal stem cells (ADMSCs) on ovarian damage induced by cyclophosphamide (CTX) and its mechanism.
 Methods: ADMSCs isolated from adipose tissue of female SD rats were cultured and divided into a blank group and a CTX group (n=15 in each group). CTX (75 mg/kg) was injected intraperitoneally to establish a model of ovarian damage in rats. A total of 45 female SD rats were also divided into 3 groups Group A (15 rats, only injected intraperitoneally with 75 mg/kg CTX diluted with 1 mL 0.9% saline), Group B [15 rats, injected intraperitoneally with 75 mg/kg CTX diluted with 1 mL 0.9% saline, after 4 estrus cycles, injected 0.6 mL ADMSCs (6×105 cells) by the tail vein], and Group C [15 rats, injected intraperitoneally with 75 mg/kg CTX diluted with 1 mL 0.9% saline, after 4 estrus cycles, injected 40 mL ADMSCs (20 mL per side, 2×104 cells) in situ ovarian]. After 4 estrus cycles, the changes of quality of life, ponderal growth were recorded, the sex hormone levels [estradiol (E2), follicle-stimulating hormone (FSH)] were tested by ELISA, and the morphology of ovarian tissue and follicle count were observed by HE staining. The expression of BMP-15, Bcl-2 and Bax in ovarian tissues were tested by immunohistochemistry, real-time PCR or Western blotting. The apoptosis rate of follicular cells was detected by TdT-mediated dUTP nick end labeling (TUNEL) assay.
 Results: After transplantation of ADMSCs, compared with the Group A, their quality of life of rats in the Group B and C was improved, and the ponderal growth was increased (both P0.05).
 Conclusion: ADMSCs transplantation can effectively repair ovarian damage induced by CTX in rats, which may be achieved by inhibiting mitochondrial apoptosis of granulosa cells.