Nano polystyrene accelerated the reproductive toxicity induced by the Tris(1,3-dichloro-2-propyl) phosphate via Nhr-69-PISD-Drp-1-mediated mitochondrial fragmentation in Caenorhabditis elegans.

Plastic products can degrade into micro/nano plastics (MNPs), which have the potential to adsorb Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) from the environment, thereby creating biological co-exposure risks. Current researches indicate that TDCPP has endocrine-disrupting effects. However, the potential toxicities associated with the co-exposure to TDCPP and MNPs remain largely unclear. In this study, we investigated the reproductive toxicity and underlying mechanisms of co-exposure to environmental concentrations of TDCPP and nano polystyrene (NPS) in Caenorhabditis elegans. Our results indicated that TDCPP reduced the reproductive capacity of nematodes, while co-exposure to NPS exacerbated the reproductive toxicity induced by TDCPP. Mechanistically, TDCPP decreased the expression of phosphatidylserine decarboxylase (psd-1), leading to reduced phosphatidylethanolamine (PE) synthesis, which affected mitochondrial membrane formation and increased mitochondrial fragmentation by inhibiting the nuclear receptor nhr-69. Meanwhile NPS synergistically enhanced the mitochondrial fragmentation induced by TDCPP by decreasing the expression of fusion gene fzo-1, and eat-3. Consequently, our results showed that NPS had no effect on germline apoptosis; however, it intensified the germline apoptosis induced by TDCPP in C. elegans by increasing the expression levels of egl-1, ced-3, and ced-4, while decreasing ced-9 levels. Moreover, NPS increased abnormal sperm activation and could synergistically enhance the abnormal sperm activation induced by TDCPP in C. elegans by lowering the expression of spe-6, spe-8, spe-12, spe-19, spe-27, and spe-29. Our findings suggest that NPS can synergistically intensify the endocrine-disrupting effects induced by TDCPP in C. elegans. In conclusion, our study demonstrates the synergistic reproductive toxic effects between TDCPP and NPS in nematodes at environmentally relevant exposure concentrations for the first time, highlighting the ecological risks posed by combined exposures to pollutants on organisms that cannot be overlooked.