Di-(2-ethylhexyl) phthalate (DEHP) is a common plasticizer, which is known to be an environmental endocrine-disrupting chemical that can jeopardize the male reproductive system. Prepuberal exposure to DEHP leads to steroidogenesis disorders. However, the specific mechanism remains ambiguous. Therefore, Sprague Dawley (SD) rats underwent prepuberal DEHP exposure at a dose of 500 mg/kg per day through gavage. Additionally, the resulting testicular injury was evaluated to confirm the disturbed steroidogenesis. Changes in testicular histology, significant reduction of serum testosterone (P < 0.01) and luteinizing hormone (P < 0.001), and significantly decreased expressions of steroidogenic acute regulatory protein (P < 0.01) and 3-beta-hydroxysteroid dehydrogenase (P < 0.05) were found in DEHP-treated rats. DEHP exposure resulted in obvious intestinal damage and oxidative stress imbalance, primarily in the jejunum. Both the activation of the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway and alterations of microbiota profiles were observed in all three gut specimens, but were most notable in the jejunum. We hypothesize that the gut-microbiota-testis axis, which is mediated by the activation of the Nrf2 antioxidant pathway, could be involved in the dysfunction of prepuberal steroidogenesis induced by DEHP.

邻苯二甲酸二（2-乙基己基）酯 (DEHP) 是一种常见的增塑剂，众所周知，它是一种破坏环境内分泌的化学物质，会危害男性生殖系统。青春期前接触 DEHP 会导致类固醇生成障碍。然而，具体的机制仍然不明确。因此，Sprague Dawley (SD) 大鼠通过管饲法以每天 500 mg/kg 的剂量接受青春期前 DEHP 暴露。此外，对由此产生的睾丸损伤进行了评估，以确认类固醇生成受到干扰。睾丸组织学改变，血清睾酮（P < 0.01）和黄体生成素显着降低（P < 0.001），类固醇生成急性调节蛋白的表达显着降低（P < 0.01）和在 DEHP 治疗的大鼠中发现了3-β-羟基类固醇脱氢酶( P < 0.05)。DEHP 暴露导致明显的肠道损伤和氧化应激失衡，主要发生在空肠。在所有三个肠道标本中都观察到核因子-E2 相关因子 2 (Nrf2) 信号通路的激活和微生物群谱的改变，但在空肠中最为显着。我们假设由 Nrf2 抗氧化途径激活介导的肠道-微生物群-睾丸轴可能参与 DEHP 诱导的青春期前类固醇生成功能障碍。