Hyperandrogenism induces histo-architectural changes in the rat uterus

BRACHO GS; ALTAMIRANO GA; KASS L; LUQUE EH; BOSQUIAZZO VL

REPRODUCTIVE SCIENCES

SAGE PUBLICATIONS INC

Lugar: Thousand Oaks, California.; Año: 2019 vol. 26 p. 657 - 668

1933-7191

The effects of androgens on the uterus have been poorly studied and they need to be clarified to 51 understand why androgen excess, such as observed in women with polycystic ovary syndrome 52 (PCOS), is a risk factor for the development of endometrial hyperplasia, cancer and infertility. 53 Thus, uterine histomorphology in a PCOS-experimental model was evaluated. Beginning at 54 weaning, female rats were injected daily with dehydroepiandrosterone (DHEA, 6 mg/100 g body 55 weight) or vehicle (sesame oil) for 20 consecutive days. On postnatal day 41 (PND41) DHEA-56 treated animals showed high serum testosterone levels. In addition, uterine histological analysis 57 showed a significant increase in luminal epithelial height and glandular density without changes in 58 cell proliferation. The thickness of the subepithelial stroma and myometrium also increased in these 59 animals. The effect of DHEA on uterine thickness was accompanied by a significant reduction in 60 cell density in both tissue compartments (subepithelial stroma and myometrium). Cell proliferation 61 was not altered in the myometrium, whereas a decrease in the proliferative activity was seen at 62 PND41 in the subepithelial stroma of DHEA animals. The analysis of the extracellular space 63 showed that the changes in the thickness of the subepithelial stroma and myometrium were related 64 to an increase in the organization of collagen fibers and water imbibition. The latter was associated 65 with higher aquaporin 3 and 8 expression. This study provides evidence to further the understanding 66 of PCOS-associated hyperandrogenism effects on uterine architecture. This could have implications 67 for the regulation of uterine function and the development of uterine lesions.