Uterine endocrine environment in a rat PCOS model

ACOSTA MV; BRACHO GS; ALTAMIRANO GA; KASS L; BOSQUIAZZO VL

Mar del Plata

Congreso; Reunión Conjunta SAIC, SAI, FAIC, SAFIS; 2022

This study aimed to investigate whether the development oflesions found in the uterus of rats with polycystic ovary syndrome (PCOS) isassociated with changes in the local endocrine environment. Female Wistar ratswere treated subcutaneously with sesame oil (CONTROL) or dehydroepiandrosterone6mg/100g of body weight (PCOS) from 21 to 40 days of age. After 24 hours, bloodand uterine horns were collected. To analyze the uterine endocrine environment inthese animals, the levels of steroid hormones [estrone (E1), estradiol (E2),progesterone (P4), and testosterone (T)] were measured in uterine tissue andserum. Also, the main steroidogenic proteins [steroidogenic acute regulatoryprotein (StAR), 17b-hydroxysteroid dehydrogenase isoform 2 (17b-HSD2),5a-reductase isoform 1 (SRD5A1) and aromatase (P450arom)] and the expression ofestrogen alpha (ESR1), progesterone (PR) and androgen (AR) receptors werestudied in the uterus. The PCOS group showed no difference in serum levels ofE2 and P4 compared to CONTROL, however, an increase in T levels was observed.In uterine tissue, E1, E2, and P4 were detected in all CONTROL animals. In thePCOS group, E2 was detected in 100%, E1 in 75%, and P4 in only 50% of the rats.Notably, T was detected in 66.7% of CONTROL, however, was not found in PCOSanimals. In addition, we observed decreased mRNA levels of StAR and increasedexpression of 17b-HSD2, SRD5A1, and P450arom in the uterus of PCOS rats.Regarding steroid receptors, only AR expression was modified, increasing in thesubepithelial stroma and myometrium of the PCOS group. Our results suggestthat, in the uterus of PCOS rats, androgens and estrogens come from systemichormonal metabolism, not from de novo synthesis since StAR wasdecreased. Also, the undetectable T levels, the increase in P450arom, togetherwith a lower P4 detection, suggest that P4 would not sufficiently counteractestrogenic stimulation, which could promote the development of uterine lesions.