Uterine histopathology and steroid metabolism in a polycystic ovary syndrome rat model

GISELA SOLEDAD BRACHO; MARÍA VIRGINIA ACOSTA; GABRIELA ANAHÍ ALTAMIRANO; ALCARÁZ, MIRTA R.; MILAGROS MONTEMURRO; CULZONI, MARIA JULIA; MARÍA FLORENCIA ROSSETTI; LAURA KASS; ENRIQUE HUGO LUQUE; VERÓNICA LIS BOSQUIAZZO

Molecular and Cellular Endocrinology

Elsevier Ireland Ltd

Año: 2024 vol. 585

The aim of this study was to investigate uterine lesions, uterine endocrine status and expression of genes involvedin uterine differentiation in a rat model of polycystic ovary syndrome (PCOS). The possible involvement of theandrogen receptor (AR) was also investigated. PCOS rats showed an increased incidence of uterine epithelial andglandular lesions and elevated serum testosterone level, which was not detected in uterine tissue. Uterine 17β-estradiol, estrone and progesterone were detected in 100%, 75% and 50% of the animals, respectively. This wasassociated with a decrease in Star and an increase in Hsd17b2, Srd5a1 and Cyp19a1, suggesting that uterinesteroids are not synthesized de novo in PCOS and that alterations in these enzymes may explain the absence oftestosterone and low progesterone. In addition, ESR2 decreased and AR increased, suggesting possible steroidreceptor crosstalk. Genes associated with uterine differentiation, PTEN and WNT5a, also showed reducedexpression. PCOS rats treated with flutamide, an AR antagonist, were similar to PCOS rats in terms of uterinelesions, serum steroid levels, ESR2, PTEN and WNT5a expression. However, testosterone, AR and aromataselevels were similar to control rats, with decreased expression of ESR1 and HOXA10, suggesting that these expressionsare AR dependent. Our results suggest that the primary cause of the observed uterine lesions in thePCOS rat model is the altered endocrine status and consequently changes in genes related to uterinedifferentiation.