Technical-grade chlordane compromises rat Sertoli cells proliferation, viability and metabolic activity

摘要

Environmental contaminants are a daily presence in human routine. Multiple studies highlight the obesogenic activity of some chemicals. Moreover, these compounds have been suggested as a cause of male subfertility and/or infertility. Technical-grade chlordane (TGC) is classified as an endocrine-disruptor chemical, while its classification as obesogen is controversial. Herein, we studied the influence of TGC on Sertoli cells (SCs) metabolism. Rat Sertoli cells (rSCs) were cultured without and in the presence of increasing concentrations (1, 10 and 1000 nM) of TGC. The viability, proliferation, metabolic activity and the metabolic profile of rSCs was assessed. Expression of key glycolysis-related enzymes, transporters and biomarkers of oxidative damage were also evaluated. Our results show that exposure to higher concentrations of TGC decreases SCs proliferation and viability, which was accompanied by increased glucose consumption associated with an upregulation of Glut3 levels. As a result, pyruvate/lactate production were enhanced thus increasing the glycolytic flux in cells exposed to 1000 nM TGC, although lactate dehydrogenase expression and activity did not increase. Notably, biomarkers associated with oxidative damage remained unchanged after exposure to TGC. This is the first report showing that TGC alters glucose rSCs metabolism and the nutritional support of spermatogenesis with consequences for male fertility.