The Effect of Erythropoietin in Preventing Ischemia-Reperfusion Injury in Ovarian Tissue Transplantation.

Abstract

Ovarian tissue cryopreservation and transplantation are the only options accepted for prepubertal girls and women requiring immediate chemotherapy. Ischemia-reperfusion injury is the main obstacle for ovarian tissue transplantation. In the present study, we aimed to evaluate the effects of recombinant human erythropoietin (EPO) on tissue viability in autotransplanted rat ovaries. Seventeen female rats were randomized into 3 groups as sham control group (n = 5), EPO-treated group (n = 6), and EPO-untreated group (n = 6). Both ovaries were excised and transplanted into a subcutaneous pouch formed at the anterior abdominal wall in the EPO-treated and untreated groups. In the EPO group, 5000 U/kg EPO was applied as local injection to the site that ovarian tissue was placed and the dose was repeated with the same route at the end of the fourth week. After 2 months, ovaries were removed and blood samples were obtained. Levels of estradiol (E2), vascular endothelial growth factor (VEGF), VEGF-C, and lipid hydroperoxidase (LPO) and the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) were measured both in blood and tissue samples. Histopathological and morphometric analyses were also performed on tissue samples. Considering serum levels, mean CAT was significantly higher ( P = .003) and mean SOD ( P = .033), LPO ( P = .050), VEGF ( P = .001), and VEGF-C ( P = .024) were significantly lower in the EPO-treated group than in the untreated group. Mean serum GPX levels were similar. Significantly higher levels of E2 were determined in the EPO group than in the untreated group. Highest serum E2 levels were found in the sham group ( P = .001). Tissue levels of GPX (1.23) and CAT (53.17) were significantly higher in the EPO group ( P = .002 and P = .001, respectively). However, tissue levels of SOD and LPO, VEGF, and VEGF-C levels were significantly lower in the EPO group than those in the untreated group ( P = .033, P = .050, P = .002, and P = .003, respectively). In tissue examination, the highest values of x, y axis and epithelial height were in the sham group. Mean value of the EPO group was found statistically significantly higher than that of the untreated group ( P ≤ .05). In terms of antral follicle count, ordering was found as sham > EPO-treated > EPO-untreated group. Follicle counts in the EPO group were significantly higher than those in the untreated group ( P ≤ 0.05). Erythropoietin improved the survival of follicles in ovarian grafts most likely by reducing ischemic injury, by improving neoangiogenesis, and by its antioxidant effects.