Premature ovarian failure occurs in about 1% of the female population under the age of 40, leading to menopausal symptoms, many systemic and psychological effects, and complications. Human amniotic membrane-derived stem cells (hAM-MSCs) and adipose tissue-derived stem cells (AD-MSCs) can differentiate into multiple cell lineages and thus their use for improving the ovarian function was an important hope in these patients. We aimed to evaluate the efficacy of hAM-MSCs in the treatment of cyclophosphamide-induced ovarian failure (IOF) in rats and compare them with AD-MSCs.
Materials and methods
Fifty adult female rats were included in the study; 10 were used as a negative control group. The other 40 rats were injected with cyclophosphamide to induce ovarian failure. Two rats were killed to confirm pathological ovarian failure. The others (38 rats) were further subdivided randomly into four groups: chemotherapy-IOF through the intraperitoneal route (IOF group), the IOF+PBS group, the IOF+AM-MSCs group, and the IOF+AD-MSCs group. Serum levels of follicle-stimulating hormone (FSH) and estradiol (E2) were estimated by enzyme-linked immunosorbent assay twice in all the rats. Also, histopathological examination of the ovarian tissues was performed and gene expressions of Oct-4, Stra8, and integrin β-1 genes were examined by qRT-PCR.
Rats with IOF showed decreased follicles and increased interstitial fibrosis, with a significant decrease in serum E2, significant increase in the serum FSH level, and significant downregulation of Stra8 and integrin β-1, with a nonsignificant decrease in the expression of Oct-4. In contrast, in the MSCs-treated groups, there were increased follicles and corporae with evident presence of oocytes with a significant increase in serum E2, a significant (in the AM-MSCs group) or a nonsignificant (in AD-MSCs group) decrease in serum FSH levels and upregulation of the three genes, with higher levels in the group that received AM-MSCs than the group that received AD-MSCs compared with the IOF group.
The current study proved that administration of either hAM-MSCs or AD-MSCs exerts a therapeutic effect on the chemotherapy-induced ovarian insult in rats, improving both hormonal and reproductive functions of the ovary, with higher efficacy of hAM-MSCs in that field.