Prenatal Hyperandrogenism Causes Uterine Alterations In a Murine Model Of Polycystic Ovary Syndrome

SILVANA ROCÍO FERREIRA; ALICIA ALEJANDRA GOYENECHE; ALICIA BEATRIZ MOTTA; CARLOS MARCELO TELLERIA

Washington DC

Congreso; 50th Annual Meeting of the Society for the Study of Reproduction; 2017

Society for the Study of Reproduction

Polycystic Ovary Syndrome (PCOS) is a common endocrine system disorder occuring among women of reproductive age. The syndrome is defined by oligo or anovulation, ovarian cysts and/or hyperandrogenism. It is also associated with several conditions such as insulin resistance, metabolic syndrome, obesity, type 2 diabetes, heart disease, mood disorders, inflammation and infertility. Prenatal hyperandrogenism is hypothesized as one of the main factors contributing to PCOS. Thus, we aimed to study the impact of prenatal hyperandrogenism on the histo-functional development of the rat uterus when adult. By using a PCOS murine model in which pregnant Sprague-Dawley rats were prenatally hyper-androgenized between days 16 to 19 of pregnancy with 1 mg of testosterone. A control group was generated by vehicle injection (vegetable oil). The prenatally hyper-androgenized female offsprings (N=120) and control offsprings (N=80) were characterized according to the estrous cycle as ovulatory or anovulatory (arrested in diestrous stage) phenotypes by collecting vaginal smears from days 45 to 90. All animals were sacrificed in diestrous stage at 90 days of life. Testosterone and estradiol serum levels were measured by radioimmunoassay. One uterine horn was dissected, fixed and embedded in paraffin for hematoxilin-eosin (H&E) staining and immunohistochemistry purposes, and the other horn was homogenized and prepared for western blot analysis. The glandular density of the sub-epithelial and stromal compartments were evaluated in histological sections upon H&E staining. Expression of cell cycle inhibitor p27kip1, and of androgen receptor (AR), were also assessed by western blot, whereas their localization within all uterine compartments was studied by immunohistochemistry. In three independent repetitions, control rats showed (100%) regular estrous cycles; 43-51% of the prenatally, hyper-androgenized group, showed irregular estrous cycles, whereas, 27-39% presented anovulatory cycles. Testosterone levels were increased in both, ovulatory and anovulatory groups (p