Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China.
The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, New York, NY, USA.
Adv Exp Med Biol. 2021;1288:307-319. doi: 10.1007/978-3-030-77779-1_15.
The testis is one of the organs in the mammalian body that is sensitive to toxicants. Accumulating evidence has shown that human exposure to toxic ingredients in Traditional Chinese Medicine (TCM), such as triptolide, gossypol, cannabidol, piperine, α-solanine, matrine, aristolochic acid, and emodin, lead to testis injury and reproductive dysfunction. The most obvious phenotype is reduced sperm counts due to defects in spermatogenesis. Studies have also shown that Sertoli cells in the seminiferous tubule, the functional unit of the testis that supports spermatogenesis, are the cell type that is most sensitive to the disruptive effects of toxicants. Since Sertoli cells are the "mother cells" that nurture germ cell development, Sertoli cell injury thus leads to failure in germ cell development in the seminiferous epithelium. Mounting evidence has shown that the Sertoli cell cytoskeletons, mitochondria function, Leydig cells steroidogenesis pathways and sperm ion channels are some of the prime targets of toxicants from TCM. We carefully evaluate recent findings in this area of research herein, and to provide a summary of these findings, including some insightful information regarding the underlying molecular basis of toxicant-induced testis injury that impede spermatogenesis.
睾丸是哺乳动物体内对毒物敏感的器官之一。越来越多的证据表明,人类接触中药(TCM)中的有毒成分,如雷公藤红素、棉酚、大麻二酚、胡椒碱、α-茄碱、苦参碱、马兜铃酸和大黄素,会导致睾丸损伤和生殖功能障碍。最明显的表型是由于精子发生缺陷导致精子数量减少。研究还表明,支持精子发生的睾丸生精小管中的支持细胞是对毒物的破坏作用最敏感的细胞类型。由于支持细胞是滋养生殖细胞发育的“母细胞”,因此支持细胞损伤会导致生精上皮中的生殖细胞发育失败。越来越多的证据表明,TCM 中的毒物主要靶向支持细胞细胞骨架、线粒体功能、间质细胞类固醇生成途径和精子离子通道。我们在此仔细评估该研究领域的最新发现,并提供这些发现的总结,包括一些关于毒物诱导的睾丸损伤阻碍精子发生的潜在分子基础的有见地的信息。