Oleuropein Ameliorates Ovarian Damage Induced By Ionizing Irradiation In A Rat Model

Obsjective In the present study,we investigated the impact of oleuropein treatment on irradiation-induced ovarian injury in a rat model and the underlying mechanism of oleuropein in protecting ovary from the deleterious damage of irradiation.Method sixty-four healthy female Sprague-Dawely rats were assigned to four groups randomly,each group included 16 animals.A(control group),B(oleuropein group),C(irradiated group),D(oleuropein + irradiated group).Oleropein was diluted with distilled water to obtain suspension at the desired concentrations(1g/100ml).Rats in group A and C both received distilled water as vehicle intragastrically(in a dose of 1ml/100 g body weight)and Rats in group B and D both received oleuropein(in a dose of 100 mg/kg body weight)once a day orally using intragastric intubation for 4 weeks.After 2 weeks,when the rats in group C and D were in the estrus,put them into cage separately and exposed to whole body irradiation at a single dose of 5 Gy 6MV X-ray.7 days after radiation exposure,8 rats chose from each group randomly were sacrificed and the serum levels of E2,FSH,LH,AMH,IL-1,IL-6 and TNF-? were elevated.Also,the ovaries were dissected and processed for histopathological evalution and counting the numbers of per follicle category after hematoxylin and eosin staining.Two week after radiation exposure,we detected vaginal cyclicit by vaginal smear.A month later,fertility experiments were carried out.Result Compared with the control group,the elevated serum levels of AMH show a decrease in irradiated group(P<0.05).But,there were no statistically significant difference between the two groups on the serum levels of E2,FSH and LH.The control group had nomal estrous cycles.But in irradiated group,3 rats had irregular estrous cycle.In irradiated group,the total numbers of ovarian follicles was decreased(P<0.05),especially for primordial and primary follicles.Simultaneously,we could find numerous atresia follicle in irradiated group(P<0.05).Contrasted with the control group,serum IL-1,IL-6 and TNF-? of irradiated group were incresed(P<0.05).Fertility experiment carried out a month later suggested that the pregnancy rate of irradiated group and the numbers of newborn rats were less than control group.When compared with irradiated group,the elevated serum levels of AMH show a increase in oleuropein +irradiated group(P<0.05).But,no significant change were found in the serum levels of E2,FSH and LH.All rats in oleuropein + irradiated group had normal estrous cycles.The morphometric analysis of follicles suggested that the irradiated rats co-treated with oleuropein showed higher numbers of ovarian follicles than irradiated group(P<0.05),especially for primary follicles.But atresia follicles showed a decrease as compared to irradiated group(P<0.05).In accordance with the irradiated group,serum levels of IL-1,IL-6 and TNF-? in oleuropein +irradiated group was decrease(P<0.05).Fertility experiment carried out a month later suggested that there were no difference among the two groups in pregnancy rate(P>0.05).But the numbers of infant rats were diferent statistically,rats in oleuropein + irradiated group had more offspring.Conclution Oleuprotein ameliorated inflammatory cascades associated with irradiation through decresing inflammatory factors IL-1,IL-6 and TNF-?.Simultaneously,it protected and restored ovarian function by increasing AMH secretion,alleviating follicle loss and improving fertility.