LONG-TERM EFFECTS OF POLYCYSTIC OVARY SYNDROME ON THE ENDOCRINE STATUS OF THE RAT UTERUS

IÑIGUEZ, INRI; BRACHO, GISELA S; ACOSTA, MARÍA V; BOSQUIAZZO, VERÓNICA LIS

Mar del Plata

Congreso; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2023

Sociedad Argentina de Investigación Clínica (SAIC)

Women with polycystic ovarian syndrome (PCOS) have a high risk of endometrial hyperplasia and cancer. These effects could be associated with alterations in the tissue metabolism of steroid hormones. The objective of this study was to investigate how long-term PCOS affects the uterus of rats. Female Wistar rats were treated subcutaneously with sesame oil (CONTROL group) or dehydroepiandrosterone 6 mg/100 g body weight (PCOS group) from 21 to 40 days of age. Then, the rats remained without any treatment. At 24 months, blood and uterine horns were collected. To analyze the endocrine environment in these animals we evaluated: a) serum levels of estradiol (E2), progesterone (P4) and testosterone (T), b) expression of uterine steroidogenic enzymes: steroidogenic acute regulatory protein (StAR), 17b-hydroxysteroid dehydrogenase isoform 1-3 (17b-HSD1, 17b-HSD2 and 17b-HSD3), 5a-reductase isoform 1 (SRD5A1), aromatase (P450arom) and steroid sulfatase (STS), and c) expression of uterine steroid receptors: estrogen alpha (ESR1) and beta (ESR2), progesterone (PR) and androgen (AR) receptors. The PCOS group showed no differences in serum E2 and T levels compared to CONTROL, however, a decrease in P4 levels was observed. The uterine expression of StAR, 17b-HSD1, 17b-HSD2, 17b-HSD3 and P450arom was similar between groups, but an increase of SRD5A1 and STS mRNA expression was demonstrated in PCOS. Regarding steroid receptors, no changes were observed in ESR1, ESR2 and PR, however, AR decreased in PCOS rats. These results suggest that the uterus of PCOS rats is exposed to higher estrogenic effects due to increased STS that increase active estrogen levels and decreased P4 levels that do not oppose estrogen stimuli. This endocrine state could be contributing to the development of uterine lesions.