Effects of chronically exogenous oxytocin on ovary and uterus: A comparison of intraperitoneal and intranasal administration

Abstract

Oxytocin (OT) has been studied as a therapeutic neuropeptide in various diseases, but its effect on the ovary and uterus is not fully known. This study investigates the effects of intranasal and intraperitoneal OT administration on ovaries and uterus in rats. Four experimental groups were created using 7-week-old Sprague Dawley-type female rats: Control (Ctrl), oxytocin-intraperitoneal (0.1 µg/day) (OT-IP), oxytocin-intranasal (0.05 µg/day) (OT-IN1), and oxytocin-intranasal (0.1 µg/day) (OT-IN2). The blood, the ovarian, and the uterus were collected at the end of the 28th day of OT administration. Afterward, histological and biochemical analyses were performed. We observed that the Graaf follicles were higher in both OT-IN2 and OT-IP groups compared to the Ctrl group. Moreover, the corpus luteum was increased only in the OT-IN2 group. Ki-67, CD31, VEGF, and TGF-ß immunostaining showed no significant change in the ovary. In contrast, Ki-67, VEGF, and OTR expressions demonstrated significant alterations in the uterus. Furthermore, TGF-ß immunohistochemistry and the histopathologic score did not reveal the statistical change in the uterus. Serum hormone levels showed that the anti-Müllerian hormone increased in all OT groups vs. the Ctrl. OT-IP showed an increment of follicle-stimulating hormone and estradiol decrement. There was a decrease in serum E2 levels, although the Graaf follicle number increased in OT-IP groups compared to the Ctrl group. However, luteinizing hormone, gonadotropin-releasing hormone, progesterone, testosterone, OT levels, and oxidative stress index did not reveal any statistical difference. Accordingly, the intranasal route may have beneficial effects compared to the intraperitoneal route regarding exogenous OT administration-related studies. In conclusion, we reported that exogenous OT increases the follicle reserve and may cause histological changes in the reproductive system of female rats.