Role of mesenchymal stem cell therapy in restoring ovarian function in a rat model of chemotherapy-induced ovarian failure: a histological and immunohistochemical study

ABSTRACT

Chemotherapeutic treatment of breast cancer in women causes damage to the reproductive system, which might result in premature ovarian failure [OF]. The present study was carried out to examine the role of mesenchymal stem cell [MSC] transplantation on ovarian function using a rat model of chemotherapy-induced OF. Twenty-six adult female albino rats were divided into two groups. Group I served as the control group. In group II, OF was induced by injecting rats with cyclophosphamide intraperitoneally with an initial loading dose of 50 mg/kg, followed by a dose of 8 mg/kg every 2 weeks for two doses by an intrape-itoneal [IP.] injection. In subgroup I la, rats received cyclophosphamide therapy for 1 month. They were left untreated for a further 1 month [OF nontreated] and were sacrificed 2 months from the start of the experiment. The rats of subgroup lib were injected with MSCs after induction of OF and were sacrificed 1 month after stem cell therapy, that is 2 months from the start of the experiment. Vaginal smears were performed and hormonal profile of serum estradiol [E2], follicle stimulating hormone [FSH], and lutenizing hormone [LH] was measured. Ovarian sections were subjected to H and E, Masson's trichrome, MSC marker CD44, and proliferating cell nuclear antigen [PCNA] immunostaining. The mean number of primordial follicles, mean area% of collagen fibers, mean number of CD44 immunopositive cells, and the mean area% of positive immunoreactivity for PCNA were measured using image analysis. The results were compared statistically. After exposure to chemotherapy, depletion of primordial follicles was observed, with the presence of many atretic follicles, congested blood vessels, and marked cortical fibrosis. Only some of the surface epithelial cells showed PCNA immunoreactivity. After MSC therapy, several primordial follicles were found in addition to secondary follicles and several corpora lutea. PCNA immunoreactivity was detected on the surface epithelium, superficial cortical oocytes, and oocytes of primordial follicles. A significant decrease in the collagen fiber content was observed. MSC transplantation could ameliorate ovarian function in rats with chemotherapy-induced OF