Zhang Qi, Xu Wei, Kong ZiYu, Wu YuJiao, Liu Yi
Department of Clinical Pharmacy, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, 445000, China.
Department of Neurology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, 445000, China.
Food Chem Toxicol. 2023 Dec;182:114181. doi: 10.1016/j.fct.2023.114181. Epub 2023 Nov 14.
Cadmium is a common environmental pollutant in daily life, the toxic mechanisms of chronic cadmium exposure on the testes have not been fully elucidated. This study aimed to explore the effects of cadmium exposure on male reproductive health and its mechanism. The results showed that cadmium exposure led widened interstitial spaces, abnormal seminiferous tubule morphology, and decreased Leydig cell numbers. Moreover, sperm quality was significantly reduced, along with a decrease in fertility rate. And cadmium exposure could activate the hypothalamic-pituitary-adrenal (HPA) axis, elevate blood glucocorticoid levels, subsequently increase glucocorticoid receptor (GR) expression and activation in testicular Leydig cells. Then GR act on the glucocorticoid receptor element (GRE) in the DNA methyltransferase 3 A (DNMT3A) promoter region and upregulate DNMT3A expression. Consequently, this led to an increase in DNA methylation levels in the angiotensin II receptor 2 (AT2R) promoter region, resulting in reduced AT2R expression and inhibiting testicular steroidogenesis. This study systematically elucidated that cadmium exposure could lead to testicular steroidogenesis suppression and decreased fertility through the GR/DNMT3A/AT2R signaling pathway. This research further provides theoretical and experimental evidence for confirming the threat of cadmium exposure to human reproduction, and contributes to the guidance and protection of male reproductive health.
镉是日常生活中一种常见的环境污染物，慢性镉暴露对睾丸的毒性机制尚未完全阐明。本研究旨在探讨镉暴露对男性生殖健康的影响及其机制。结果表明，镉暴露导致间质间隙增宽、生精小管形态异常以及睾丸间质细胞数量减少。此外，精子质量显著降低，生育率也随之下降。并且镉暴露可激活下丘脑 - 垂体 - 肾上腺（HPA）轴，提高血液中糖皮质激素水平，随后增加睾丸间质细胞中糖皮质激素受体（GR）的表达和激活。然后GR作用于DNA甲基转移酶3A（DNMT3A）启动子区域的糖皮质激素反应元件（GRE），上调DNMT3A的表达。因此，这导致血管紧张素II受体2（AT2R）启动子区域的DNA甲基化水平升高，从而导致AT2R表达降低并抑制睾丸类固醇生成。本研究系统地阐明了镉暴露可通过GR/DNMT3A/AT2R信号通路导致睾丸类固醇生成受抑制和生育力下降。本研究进一步为证实镉暴露对人类生殖的威胁提供了理论和实验依据，并有助于指导和保护男性生殖健康。
