Browsing by Author "Cardoso, Ana Margarida Nunes Ferreira Ribeiro"
Now showing 1 - 1 of 1
Results Per Page
Sort Options
- Obesogens and Male Fertility: a Threat to Sertoli Cell Function?Publication . Cardoso, Ana Margarida Nunes Ferreira Ribeiro; Cavaco, José Eduardo Brites; Oliveira, Carlos Pedro Fontes; Rato, Luís Pedro FerreiraIn the last decades, several studies evidenced a negative correlation between life expectancy and sperm quality in developed countries. Although the etiology of this trend in male fertility remains a matter of debate, environmental compounds that predispose to weight gain, namely obesogens, are appointed as pivotal contributors due to their action as endocrine disruptors. Obesogens can be found virtually everywhere, including in high-energy diets or in the surrounding environment. Tributyltin arises as the obesogen model, being considered one of the most toxic compounds ever introduced into the environment. Tributyltin presents lipophilic characteristics and high affinity to accumulate in tissues with high lipid contents, as is the case of testes. Once stored in these organs, tributyltin can affect testicular physiology and metabolism, which are crucial for spermatogenesis. Disruption of these tightly regulated metabolic pathways may be the molecular basis of adverse reproductive outcomes, such as increased oxidative stress or even sperm defects. The appropriate development of germ cells is highly dependent on the nutritional support provided by Sertoli cells, which metabolism present some unique features. Sertoli cells metabolize glucose, being the majority of it converted to lactate, the main fuel for developing germ cells. Thus, the regulation of Sertoli cell glycolytic metabolism plays a central role on spermatogenesis. Interestingly, these cells were already proven to be a target for environmental toxicants, being these compounds able to alter their structure and/or function. Herein, we evaluated the impact of tributyltin on Sertoli cell metabolism, with a particular focus on glycolytic metabolism. In order to achieve it, we selected 3 different concentrations of tributyltin: 0.1 nM, a subtoxic dose but to which weigh gain and retinoid X receptor- peroxisome proliferator-activated receptor ? activation were already described; 10 nM, a dose within the range of concentrations reported in serum and tissues of humans; and 1000 nM, a dose from which broad cytotoxic effects have already been evidenced. Our results evidenced that the exposure to the highest concentration of tributyltin (1000 nM) induce severe cytotoxic effects in rat Sertoli cells, decreasing their proliferation to 28%, when compared with the control group. Since the lower concentrations of tributyltin (10 nM and 0.1 nM) did not induced cytotoxic effects, we investigated possible changes in Sertoli cells maturation markers through the analysis of inhibin B and androgens receptor. However, for the adopted concentrations, significant changes were not observed in the expression of these transcripts. However, both concentrations (10 and 0.1 nM) revealed to affect glycolysis and lactate production-related events. Indeed, the glycolytic pathway was favored in Sertoli cells exposed to tributyltin 10 nM, since the increased glucose and pyruvate consumption was followed by an increase in lactate production. However, the protein expression of glucose transporters 1, 2 and 3 remain unaltered, while the expression of lactate dehydrogenase was decreased when compared to control. In addition, Sertoli cells exposed to this concentration of tributyltin revealed also an increased expression of monocarboxylate transporter isoform 4 when compared to control, which had probably contributed to a higher lactate export. Concerning to Sertoli cells exposed to the lowest concentration of tributyltin (0.1 nM), significant changes in glucose consumption were not observed, even though a decreased expression of glucose transporters 1 and 2 was evidenced in this experimental group. Similarly, also the pyruvate consumption was significantly lower when compared with the group of Sertoli cells exposed to tributyltin 10 nM. The absence of significant changes in lactate production may be due to the decreased lactate dehydrogenase expression. Besides, we also observed a significant decrease in alanine levels in both groups of Sertoli cells exposed to tributyltin, which favors a high cytosolic oxidative redox state, predisposing the cells to a possible oxidative environment. In conclusion, this study showed that tributyltin, in addition to induce significant cytotoxic effects in rat Sertoli cells when administered at a high dose, also promotes several changes in one of the main functions of differentiated Sertoli cells, the glycolytic metabolism. In this regard, tributyltin may affect spermatogenesis and thus male fertility.