Ji HengLi, Fan Wei, Kakar Mohibullah, Alajmi Reem Atalla, Bashir Muhammad Amjad, Shakir Yasmeen
Department of Nephrology, Huaian Cancer Hospital, Huai'an, Jiangsu, China.
Department of Laboratory Medicine, Huaian Cancer Hospital, Huai'an, Jiangsu, China.
J Exp Zool A Ecol Integr Physiol. 2024 Jan;341(1):31-40. doi: 10.1002/jez.2758. Epub 2023 Oct 20.
Cadmium is a male reproductive toxicant that interacts with a variety of pathogenetic mechanisms. However, the effect of cadmium on the regulatory mechanism of the steroidogenic pathway of Leydig cells during spermatogenesis is still ambiguous. Light microscopy, Western blot, immunohistochemistry, immunofluorescence, and quantitative polymerase chain reaction were performed to study the regulatory mechanism of the steroidogenic pathway of Leydig cells during spermatogenesis. The results indicated that in the control group, Leydig cells showed dynamic immunoreactivity and immunosignaling action with a strong positive significant secretion of 3β-hydroxysteroid hydrogenase (3β-HSD) in the interstitial compartment of the testis. Leydig cells showed a high active regulator mechanism of the steroidogenic pathway with increased the proteins and genes expression level of steroidogenic acute regulatory protein (STAR), cytochrome P450 cholesterol (CYP11A1), cytochrome P450 cholesterol (CYP17A1), 3β-hydroxysteroid hydrogenase (3β-HSD) 17β-hydroxysteroid hydrogenase (17β-HSD), and androgen receptor (AR) that maintained the healthy and vigorous progressive motile spermatozoa. However, on treatment with cadmium, Leydig cells were irregularly dispersed in the interstitial compartment of the testis. Leydig cells showed reduced immunoreactivity and immunosignaling of 3β-HSD protein. Meanwhile, cadmium impaired the regulatory mechanism of the steroidogenic process of the Leydig cells with reduced protein and gene expression levels of STAR, CYP11A1, CYP17A1, 3β-HSD, 17β-HSD, and AR in the testis. Additionally, treatment with cadmium impaired the serum LH, FSH, and testosterone levels in blood as compared to control. This study explores the hazardous effect of cadmium on the regulatory mechanism of the steroidogenic pathway of Leydig cells during spermatogenesis.
镉是一种雄性生殖毒物，可与多种致病机制相互作用。然而，镉在精子发生过程中对睾丸间质细胞类固醇生成途径调节机制的影响仍不明确。本研究采用光学显微镜、蛋白质免疫印迹法、免疫组织化学、免疫荧光和定量聚合酶链反应，研究精子发生过程中睾丸间质细胞类固醇生成途径的调节机制。结果显示，在对照组中，睾丸间质细胞呈现动态免疫反应性和免疫信号作用，睾丸间质中3β-羟基类固醇脱氢酶（3β-HSD）分泌呈强阳性显著。睾丸间质细胞显示出类固醇生成途径的高活性调节机制，类固醇生成急性调节蛋白（STAR）、细胞色素P450胆固醇侧链裂解酶（CYP11A1）、细胞色素P450 17α-羟化酶/17,20-裂解酶（CYP17A1）、3β-羟基类固醇脱氢酶（3β-HSD）、17β-羟基类固醇脱氢酶（17β-HSD）和雄激素受体（AR）的蛋白质和基因表达水平升高，从而维持健康且活力旺盛的进行性运动精子。然而，镉处理后，睾丸间质细胞在睾丸间质中不规则分散。睾丸间质细胞显示3β-HSD蛋白的免疫反应性和免疫信号减弱。同时，镉损害了睾丸间质细胞类固醇生成过程的调节机制，睾丸中STAR、CYP11A1、CYP17A1、3β-HSD、17β-HSD和AR的蛋白质和基因表达水平降低。此外，与对照组相比，镉处理损害了血液中的血清促黄体生成素（LH）、促卵泡生成素（FSH）和睾酮水平。本研究探讨了镉在精子发生过程中对睾丸间质细胞类固醇生成途径调节机制的有害影响。
