The epididymis as a target of endocrine disruption: a metabolic perspective

• Autor(a) principal: Tavares, Daniel Alexandre Ferreira
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/12538
• topic: (in)Fertilidade Masculina; Desreguladores Endócrinos; Epidídimo; Metabolismo; Vinclozolina; Domínio/Área Científica::Engenharia e Tecnologia::Bioquímica

Male fertility depends on the output of spermatogenic processe, as well as on the maturation events occurring during sperm passage throughout the epididymis. Epididymis plays an important role in storage of sperm, and also increasing their concentration and providing immunological and oxidative stress protection. In order to perform its functions, the epididymis depends on glucose metabolism as energy source, and also contributes by its secretory activity to establish the composition of the epididymal fluid. Recently, it was demonstrated that several energy pathways are active in this organ, namely glycolysis, and several metabolites like pyruvate are detected in the epididymal fluid. Also, the epididymal milieu has been shown to be rich in lipids, a class of macromolecules that plays a crucial role in the structure of sperm membrane influencing fertilization capacity. The activity of the epididymis can be regulated by hormones, like androgens, that can also have an influence on its metabolism. Endocrine disruptors (EDCs) are exogenous compounds capable of perturbing the normal hormone signalling. The EDC vinclozolin (VNZ) acts as anti-androgen and has been shown to affect male reproduction. However, the effect of VNZ in the epididymis, namely in the deregulation of metabolism is largely unknown. The present dissertation investigates the impact of VNZ exposure in the rat epididymis glycolytic and lipidic metabolism. For this purpose, caput epididymis sections were cultured ex vivo in the presence or absence of VNZ 500 µM. Glucose consumption, lactate production, and the expression and activity of glycolytic and lipid metabolism regulators were evaluated by spectrophotometric assays and Western blot analysis. The results obtained showed that VNZ increased glucose consumption in the caput epididymis, whereas decreasing lactate production. Also, VNZ activated both fatty acid biosynthesis and degradation. These findings first demonstrated that VNZ disrupts glycolytic and lipid metabolism in the epididymis and highlight for the impact that this and others EDCs may have affecting sperm quality and male fertility.