Abstract：
Tetrachlorobisphenol A (TCBPA), a halogenated flame retardant and endocrine disruptor, has been detected in human urine and serum. While previous research has shown its impact on the reproductive system, investigations into its mechanisms during puberty remain limited. This study aims to explore the effects of TCBPA on Leydig cells in adolescent mice and potential underlying mechanisms. Male C57 mice of age 28 days were gavaged with 50, 100, and 200 mg/kg/day for 28 days. TCBPA did not alter body weight and testis weight but lowered testosterone levels at 100 and 200 mg/kg and reduced sperm count in the epididymis at 200 mg/kg. TCBPA lowered Leydig cell number at 200 mg/kg while it downregulated key Leydig cell gene (Lhcgr, Scarb1, Cyp11a1, Cyp17a1, Hsd3b6, Hsd17b3 and Insl3) as low as 50 mg/kg. Further study indicated that TCBPA induced reactive oxygen species and caused endoplasmic reticulum stress. In vitro study in TM3 mouse Leydig cells showed that TCBPA indeed induced reactive oxygen species and caused endoplasmic reticulum stress at 75 μM and inhibited testosterone production at this concentration and addition of antioxidant tocopherol can reverse it. These discoveries provide new insights and references for a deeper understanding of the toxic mechanisms of TCBPA on Leydig cells during puberty.
摘要：
四氯双酚A(TCBPA),卤化阻燃剂和内分泌干扰物，已在人体尿液和血清中检测到。虽然以前的研究表明它对生殖系统的影响，对其青春期机制的调查仍然有限。本研究旨在探讨TCBPA对青春期小鼠睾丸间质细胞的影响及其潜在机制。28日龄的雄性C57小鼠用50、100和200mg/kg/天的剂量给药28天。TCBPA不会改变体重和睾丸重量，但会降低100和200mg/kg的睾丸激素水平，并降低200mg/kg的附睾精子数量。TCBPA降低了200mg/kg的Leydig细胞数量，同时下调了关键的Leydig细胞基因（Lhcgr，Scarb1，Cyp11a1，Cyp17a1，Hsd3b6，Hsd17b3和Insl3）低至50mg/kg。进一步研究表明，TCBPA可诱导活性氧并引起内质网应激。在TM3小鼠Leydig细胞中进行的体外研究表明，TCBPA确实在75μM时诱导了活性氧并引起内质网应激，并且在此浓度下睾丸激素抑制了生产，添加抗氧化剂生育酚可以逆转它。这些发现为更深入地了解TCBPA对青春期Leydig细胞的毒性机制提供了新的见解和参考。
