Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal; Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal.
Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal.
Toxicol In Vitro. 2020 Mar;63:104673. doi: 10.1016/j.tiv.2019.104673. Epub 2019 Nov 5.
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.
环境污染物是人类日常生活中的常见存在。多项研究强调了一些化学物质的致肥胖活性。此外,这些化合物被认为是男性生殖力低下和/或不育的原因之一。技术级氯丹(TGC)被归类为内分泌干扰化学物质,而其作为致肥胖物的分类仍存在争议。在此,我们研究了 TGC 对支持细胞(SCs)代谢的影响。培养大鼠支持细胞(rSCs),并在存在不同浓度(1、10 和 1000 nM)TGC 的情况下进行培养。评估 rSCs 的活力、增殖、代谢活性和代谢谱,以及关键糖酵解相关酶、转运蛋白和氧化损伤生物标志物的表达。我们的结果表明,暴露于较高浓度的 TGC 会降低 SCs 的增殖和活力,这伴随着葡萄糖消耗的增加,与 Glut3 水平的上调有关。结果,丙酮酸/乳酸的产生增加,从而增加了暴露于 1000 nM TGC 的细胞中的糖酵解通量,尽管乳酸脱氢酶的表达和活性没有增加。值得注意的是,暴露于 TGC 后与氧化损伤相关的生物标志物没有变化。这是第一个表明 TGC 改变 rSCs 葡萄糖代谢和生精营养支持从而影响男性生育力的报告。