Prenatal kisspeptin antagonist exposure prevents polycystic ovary syndrome development in prenatally-androgenized rats in adulthood: An experimental study

Background: Increased levels of kisspeptin are associated with hypothalamus-pituitary-ovary axis dysfunction. It may lead to the development of polycystic ovary syndrome (PCOS). Objective: We aimed to investigate the effect of prenatal kisspeptin antagonist exposure on the development of PCOS in prenatally androgenized rats in adulthood. Materials and Methods: In this experimental study, pregnant rats were injected with free testosterone (T, ۵ mg/day) or T+P۲۷۱ (kisspeptin antagonist) on the ۲۰th day of the pregnancy period (n = ۵ in each group), while rats in the control group received solvent. Female offspring were examined in terms of anogenital distance (AGD), anovaginal distance (AVD), vaginal opening, serum total testosterone (TT) levels, ovarian follicles, and the regularity of estrous cycles in adulthood. AGD and AVD were measured using a vernier caliper. TT levels were measured using the enzyme-linked immunosorbent assay method. Ovaries were fixed in ۱۰% formalin, tissue processing was done by a standard protocol, and then ovaries embedded in paraffin. ۵ μm-thickness ovarian sections mounted on a glass slide, deparaffinized, and stained using Harris’s Hematoxylin and Eosin Y. Results: AGD, AVD (p < ۰.۰۰۱), TT levels (p = ۰.۰۲), and the numbers of preantral and antral follicles (p < ۰.۰۰۱) in the ovaries were significantly decreased in prenatally T-P۲۷۱-exposed rats compared to prenatally T-exposed rats. The age of vaginal opening was early in T-P۲۷۱-exposed rats compared to prenatally T-exposed rats (p < ۰.۰۰۱). The number of corpora lutea was significantly increased in T-P۲۷۱-exposed rats (p < ۰.۰۰۱). No cystic follicles were observed in the ovaries of prenatally T-P۲۷۱-exposed rats. Prenatally T-P۲۷۱-exposed rats had regular estrous cycles compared to prenatally T-exposed rats. Conclusion: Prenatal exposure to kisspeptin antagonist can prevent PCOS development in prenatally androgenized rats in adulthood.

کلیدواژه ها:

Androgen ، Kisspeptin antagonist ، Polycystic ovary syndrome ، Rat. ، آندروژن ، آنتاگونیست کیس پپتین ، سندرم تخمدان پلی کیستیک ، موش آزمایشگاهی.