Polystyrene nanoplastics exacerbated the toxicity of cadmium: from the perspective of the placenta-uterus micro-environment

Heavy metal and plastic pollution are one of most serious environmental problems, which threaten ecological environment and human health. Herein, plastics could be aged fragmented to nanoplastics (NPs) and Cadmium (Cd) as one of the most prevalent heavy metals was found in polluted soil in China. Additionally, Cd and NPs are widespread coexistence in aquatic and mammals. Additionally, the rate of premature births and the death of infants is increasing, and environmental pollution is one of main factors. Therefore, the impact of environmental pollution on pregnant women deserves more attention. In this study, the pregnant C57BL/6 J mice were exposed to PS-NPs and/or Cd from gestational day 0.5 to 15.5, and we explored the impact and potential mechanism of maternal co-exposure to PS-NPs and Cd on placenta-uterus micro-environment in mice and using inhibitors for verification. The results indicated that co-exposure PS-NPs and Cd caused more serious impairment in gut, placenta and uterus barrier, promoted more Cd accumulation, and affected the metal transporters and the homeostasis of glycolipid metabolism, thereby inducing mtROS mediated excessive Mitophagy, causing the impairment of uterus and placenta structure and function. Additionally, mtROS and VDAC1 plays a vital role in this process via inhibitors intervention. Generally, we have proven that PS-NPs can adsorb Cd, impair the uterine-placental barrier, thereby promoting the accumulation of Cd and mtROS mediated VDAC1-mitophagy is the key signal pathway for the adverse effects caused by Cd and PS-NPs co-exposure during pregnancy.