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The aim of this study was to investigate uterine lesions, uterine endocrine status and expression of genes involved in uterine differentiation in a rat model of polycystic ovary syndrome (PCOS). The possible involvement of the androgen receptor (AR) was also investigated. PCOS rats showed an increased incidence of uterine epithelial and glandular 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 was associated with a decrease in Star and an increase in Hsd17b2, Srd5a1 and Cyp19a1, suggesting that uterine steroids are not synthesized de novo in PCOS and that alterations in these enzymes may explain the absence of testosterone and low progesterone. In addition, ESR2 decreased and AR increased, suggesting possible steroid receptor crosstalk. Genes associated with uterine differentiation, PTEN and WNT5a, also showed reduced expression. PCOS rats treated with flutamide, an AR antagonist, were similar to PCOS rats in terms of uterine lesions, serum steroid levels, ESR2, PTEN and WNT5a expression. However, testosterone, AR and aromatase levels were similar to control rats, with decreased expression of ESR1 and HOXA10, suggesting that these expressions are AR dependent. Our results suggest that the primary cause of the observed uterine lesions in the PCOS rat model is the altered endocrine status and consequently changes in genes related to uterine differentiation., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest that could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2024. Published by Elsevier B.V.)

Our aim was to evaluate whether chronic administration of CAF affects the uterus and induces the morphological and molecular changes associated with endometrial hyperplasia. Female Wistar rats exposed to CAF from weaning for 20 weeks displayed increased energy intake, body weight and fat depots, but did not develop metabolic syndrome. The adult uteri showed an increase in glandular volume fraction and stromal area. The epithelial proliferation rate and protein expression of oestrogen receptor alpha (ERα) were also increased. The CAF diet enhanced leptin serum levels and the long form of leptin receptor (Ob-Rb) mRNA expression in the uterus. No changes were detected in either insulin serum levels or those of insulin growth factor I (IGF-I) mRNA expression. However the levels of IGF-I receptor (IGF-IR) mRNA were lower in CAF-fed animals. Overall, the results indicate that our rat model of the CAF diet produces morphological and molecular changes associated with uterine hyperplasia and could predispose to endometrial carcinogenesis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We evaluated the effect of cafeteria diet (CAF) on the mRNA levels and DNA methylation state of feeding-related neuropeptides, and neurosteroidogenic enzymes in discrete hypothalamic nuclei. Besides, the expression of steroid hormone receptors was analyzed. Female rats fed with CAF from weaning increased their energy intake, body weight, and fat depots, but did not develop metabolic syndrome. The increase in energy intake was related to an orexigenic signal of paraventricular (PVN) and ventromedial (VMN) nuclei, given principally by upregulation of AgRP and NPY. This was mildly counteracted by the arcuate nucleus, with decreased AgRP expression and increased POMC and kisspeptin expression. CAF altered the transcription of neurosteroidogenic enzymes in PVN and VMN, and epigenetic mechanisms associated with differential promoter methylation were involved. The changes observed in the hypothalamic nuclei studied could add information about their differential role in food intake control and how their action is disrupted in obesity., (Copyright © 2017 Elsevier B.V. All rights reserved.)