Navegando por Palavras-chave "Morfogêneses Epididimária"

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    Morfogênese epididimária: relevância funcional de androgênios e glicocorticoides
    (Universidade Federal de São Paulo (UNIFESP), 2020-07-30) Sousa, Maria Eleticia De [UNIFESP]; Winston, Maria Christina Werneck De Avellar [UNIFESP]; Universidade Federal de São Paulo
    The epididymis is a single and convoluted tubule, which connects the efferent ductules to the vas deferens. It is an important organ for sperm maturation, transport, storage, and their protection before ejaculation. The epididymal morphogenesis, that occurs from the mesonephric duct (its embryonic precursor), is primarily dependent on androgens by mechanisms that are not well defined yet. Recently, our research group has identified a differential expression pattern of glucocorticoids receptors (GR) on epithelial and mesenchymal cells of the developing rat mesonephric duct. The biological role of GR/glucocorticoid signaling, as well as its potential interaction with androgens during pre- and post-natal development of the epididymis is not well established yet. In the present study, we used a preclinical model of dexamethasone (synthetic glucocorticoid) antenatal treatment in rat dams (Wistar) as a tool to help to elucidate the role and function of glucocorticoids during the mesonephric duct development, with a focus on epididymal morphogenesis. Initially, we tested the daily DEX (1 mg/kg, s.c.) treament of dams during the gestational period that, in the rat, correlates with epididymal morphogenesis (e17.5-e19.5; group DEX-LW versus control, SAL-LW; euthanasia at e20.5). The specific aims, using this preclinical model, were: a) to evaluate the effects of the DEX antenatal treatment on (i) biometric and hormonal parameters in the dams, and (ii) biometric and hormonal parameters in the male fetuses, b) to characterize the effects of the DEX antenatal treatment on histomorphological parameters and cellular proliferation rate of the mesonephric duct of the male offsprings, c) to characterize the effects of the DEX antenatal treatment in the immunodistribution of AR and GR in the mesonephric duct of the male offsprings, d) to characterize the effect of the DEX antenatal treatments in the transcriptional levels of a subset of genes that are target of GR and AR regulation. Based on the results obtained, we subsequently conducted studies by exposing rat dams to daily DEX treatment during the gestacional period that involves masculinization and differntation windows (e13.5-e19.5; DEX-FL versus control SAL-FL; euthanasia at e20.5). Our readouts were: biometrical parameters (dams and fetuses), hormonal dosage (corticosterone and testosterone; dams and fetuses), histopathology, immunofluorescence studies and quantification of gene expression by RT-qPCR on isolated mesonephric duct. Althogether the results confirmed the hypothesis that glucocorticoids play a role in morphogenetic events of the mesonephric duct, including epididymal morphogenesis; also, the data contributed to the better understanding that changes in maternal plasma concentration of glucocorticoids impact the expression and function profile of GR and AR in the duct. From a translational point of view, the present study corroborates to a better understand of how corticotherapy or changes in the endougenous glucocorticoids profile during gestational period may influence reproductive health of male offsprings. (Research Ethics Committee, CEUA/UNIFESP, #8759031215).