Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY 10065, USA.
Trends Mol Med. 2013 Jul;19(7):396-405. doi: 10.1016/j.molmed.2013.03.006. Epub 2013 May 2.
Testes are sensitive to toxicants, such as cadmium and phthalates, which disrupt a local functional axis in the seminiferous epithelium known as the 'apical ectoplasmic specialization (apical ES)-blood-testis barrier (BTB)-basement membrane (BM)'. Following exposure, toxicants contact the basement membrane and activate the Sertoli cell, which perturbs its signaling function. Thus, toxicants can modulate signaling and/or cellular events at the apical ES-BTB-BM axis, perturbing spermatogenesis without entering the epithelium. Toxicants also enter the epithelium via drug transporters to potentiate their damaging effects, and downregulation of efflux transporters by toxicants impedes BTB function such that toxicants remain in the epithelium and efficiently disrupt spermatogenesis. These findings support a novel model of toxicant-induced disruption of spermatogenesis that could be interfered with using small molecules.
测试对有毒物质敏感，如镉和邻苯二甲酸盐，它们会破坏生精上皮中的一个局部功能轴，称为“顶端外质特化（apical ES）-血睾屏障（BTB）-基底膜（BM）”。暴露后，有毒物质接触基底膜并激活支持细胞，扰乱其信号功能。因此，有毒物质可以调节顶端 ES-BTB-BM 轴的信号和/或细胞事件，在不进入上皮的情况下扰乱精子发生。有毒物质还通过药物转运体进入上皮以增强其破坏作用，而有毒物质下调外排转运体则会阻碍 BTB 功能，使有毒物质留在上皮中并有效地扰乱精子发生。这些发现支持了一种新的有毒物质诱导精子发生破坏的模型，该模型可以使用小分子进行干扰。
