Ações da Angiotensina (1-7) em ratas com ovário policístico induzido por valerato de estradiol

Abstract

Polycystic Ovary Syndrome (PCOS) is a multifactorial endocrine condition, with a worldwide prevalence of 6 - 10%. The main findings are anovulatory cycles, infertility, menstrual irregularity and hyperandrogenism. Angiotensin 1-7 (Ang (1-7)) is the main product of the angiotensin-converting enzyme 2 (ACE2). ACE2, Ang-(1-7) and Mas receptor are present in the ovaries and are involved in the ovulatory process and steroidogenesis. Rat ovaries of a PCOS model induced by estradiol valerate (EV) showed reduced levels of Ang (1-7) and Mas. We hypothesized that Ang (1-7) treatment could reduce the features observed in the PCOS model. Thus, we evaluated the action of Ang (1-7) in rats with PCOS induced by EV. Eight-week-old female Wistar rats (Rattus novergicus) with regular estrous cycles were divided into two groups: Control (animals treated with 0.2 mL of corn oil (vehicle) and PCOS, rats treated with 2 mg of intramuscular EV diluted in 0.2 mL of vehicle. After 60 days, each group was divided into two subgroups, one treated with 30 μg/kg of Ang (1-7) and the other with 30 μg/kg of cyclodextrin, diluted in 0.5 ml of water, administered by gavage once a day, during 15 days. Estrous cycle was assessed by vaginal lavage. After treatment, the animals were euthanized in estrus by guillotine, after sedation with isoflurane. Ovaries, uterus, anterior pituitary gland, whole blood and serum were collected for histology, ELISA, PCR and Western blot analyses. The experimental protocol was approved by the Animal Use Ethics Committee (CEUA) of UFMG according to CONCEA guidelines, protocol number 134/2022 The PCOS group developed estrous cycle irregularity and ovarian cysts. Oral treatment with Ang (1-7) reduced the number of ovarian cysts induced by EV and reversed the reduction of cycles observed in the PCOS group. There was a reduction in the corpora lutea in animals in the PCOS group, but the effect was not altered by treatment with Ang (1-7). No differences between the groups were observed in healthy follicles or between the ovary and uterus weights. The reduced ovarian expression of Hsd3b observed after PCOS induction was reversed by Ang (1-7) treatment. The expression of the Star gene was higher in the ovaries of the PCOS + Ang (1-7) group compared to the PCOS + cyclodextrin group. No statistical differences were observed for Cyp19a1 and Mas genes. Ovarian expression of Ace2, increased after PCOS induction, was reversed by Ang (1-7). In the anterior pituitary gland, no differences were observed between groups for the transcripts of the Lhb and Fshb genes. LH beta subunit (LHB), determined by WB, was reduced in PCOS group and the effect not reversed by Ang (1-7). No differences were observed in blood concentrations of LH or serum levels of testosterone, estradiol and progesterone. In conclusion, Ang (1-7) treatment reversed some important ovarian features observed in the PCOS animal model induced by EV. Ang (1-7) proved to be a substance of pharmacological interest for the treatment of PCOS, but further studies are needed to better clarify the mechanisms of action.