Table1_The simultaneous administration of microplastics and cadmium alters rat testicular activity and changes the expression of PTMA, DAAM1 and PREP.DOCX

This paper confirms the damaging effects produced by MP and Cd on testicular activity in the rat. Oral treatment with both chemicals resulted in testicular damage, documented by biomolecular and histological alterations, particularly by impaired morphometric parameters, increased apoptosis, reduced testosterone synthesis, and downregulation of the steroidogenic enzyme 3β-HSD. We also demonstrated, for the first time, that both MP and Cd can affect the protein level of PTMA, a small peptide that regulates germ cell proliferation and differentiation. Interestingly, the cytoarchitecture of testicular cells was also altered by the treatments, as evidenced by the impaired expression and localization of DAAM1 and PREP, two proteins involved in actin- and microtubule-associated processes, respectively, during germ cells differentiation into spermatozoa, impairing normal spermatogenesis. Finally, we showed that the effect of simultaneous treatment with MP and Cd were more severe than those produced by MP alone and less harmful than those of Cd alone. This could be due to the different ways of exposure of the two substances to rats (in drinking water for Cd and in oral gavage for MP), since being the first contact in the animals’ gastrointestinal tract, MP can adsorb Cd, reducing its bioavailability through the Trojan-horse effect.

本研究证实了MP与镉（Cd）对大鼠睾丸功能的损伤作用。两种物质经口染毒均可引发睾丸损伤，该损伤可通过生物分子与组织学改变得到证实，具体包括形态计量参数异常、细胞凋亡水平升高、睾酮合成减少，以及类固醇生成酶3β-羟类固醇脱氢酶（3β-HSD）的表达下调。本研究还首次发现，MP与镉均可影响原胸腺素α（PTMA）的蛋白表达水平——该小分子肽可调控生殖细胞的增殖与分化过程。值得关注的是，染毒处理还会改变睾丸细胞的细胞构筑：DAAM1与PREP两种蛋白的表达及定位均出现异常，二者分别参与肌动蛋白相关过程与微管相关过程，而在生殖细胞向精子分化的阶段，这两种蛋白发挥着关键作用，最终干扰正常精子发生。最后，本研究表明，MP与镉联合染毒的损伤效应较单纯MP染毒更为严重，但毒性弱于单纯镉染毒。该现象可能与两种物质的染毒途径差异相关：镉通过饮水染毒，MP则经灌胃染毒。由于MP首先接触动物胃肠道，可通过特洛伊木马效应吸附镉，降低其生物利用度。