Abstract：
Hexavalent chromium (Cr(VI)) causes testicular damage and reduces testosterone secretion. Testosterone synthesis relies on cholesterol as a raw material, and its availability can be affected by lipophagy. However, the role of lipophagy in Cr(VI)-induced testicular damage and reduced testosterone secretion remains unclear. In this study, we investigated the effect of Cr(VI) on lipid metabolism and lipophagy in the testes of ICR mice. Forty mice were randomly divided into four groups and exposed to different doses of Cr(VI) (0, 75, 100, 125 mg/kg) for thirty days. Cr(VI) increased the rate of sperm abnormalities, decreased testosterone level, and decreased the levels of testosterone synthesis-related proteins, namely steroidogenic acute regulatory (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) proteins. Through metabolomic analysis, Oil Red O staining, and biochemical indicator (triglyceride and total cholesterol) analysis, Cr(VI) was found to disrupt testicular lipid metabolism. Further investigation revealed that Cr(VI) inhibited the AMP-activated protein kinase (AMPK)/sterol regulatory element-binding protein 1 (SREBP1) pathway, elevated levels of the autophagy-related proteins microtubule-associated protein 1 light chain 3B (LC3B) and sequestosome 1 (SQSTM1)/P62 and lipophagy-related proteins Rab7 and Rab10, while increasing colocalization of LC3B and Perilipin2. These findings suggest that Cr(VI) exposure leads to abnormal lipid metabolism in the testes by suppressing the AMPK/SREBP1 pathway and disrupting lipophagy, ultimately reducing testosterone level and inducing testicular damage.
摘要：
六价铬（Cr（VI））引起睾丸损伤并减少睾丸激素分泌。睾酮的合成依赖于胆固醇作为原料,它的可用性会受到吸脂性的影响。然而,吸脂性在Cr(VI)诱导的睾丸损伤和睾酮分泌减少中的作用尚不清楚。在这项研究中,我们研究了Cr（VI）对ICR小鼠睾丸脂质代谢和吞噬的影响。将40只小鼠随机分为四组，分别暴露于不同剂量的Cr（VI）（0、75、100、125mg/kg）30天。Cr(Ⅵ)增加精子畸形率,睾酮水平降低,并降低了睾酮合成相关蛋白的水平，即类固醇急性调节（StAR）和3β-羟基类固醇脱氢酶（3β-HSD）蛋白。通过代谢组学分析，油红O染色,和生化指标（甘油三酯和总胆固醇）分析，发现Cr（VI）破坏睾丸脂质代谢。进一步研究发现，Cr（VI）抑制AMP激活的蛋白激酶（AMPK）/固醇调节元件结合蛋白1（SREBP1）途径，自噬相关蛋白微管相关蛋白1轻链3B（LC3B）和螯合体1（SQSTM1）/P62以及脂质吞噬相关蛋白Rab7和Rab10的水平升高，同时增加LC3B和Perilipin2的共定位。这些发现表明，Cr（VI）暴露通过抑制AMPK/SREBP1途径并破坏脂质吞噬而导致睾丸中异常的脂质代谢，最终降低睾酮水平并诱导睾丸损伤。
