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Combined Effects of Polystyrene Nanosphere and Homosolate Exposures on Estrogenic End Points in MCF-7 Cells and Zebrafish
Summary
Researchers found that tiny polystyrene nanoplastics can enhance the estrogen-mimicking effects of homosalate (a common sunscreen ingredient) in human breast cancer cells and zebrafish. The nanoplastics acted as carriers, increasing cellular uptake of the sunscreen chemical and amplifying its hormone-disrupting activity. This is significant for human health because people are regularly exposed to both nanoplastics and sunscreen chemicals simultaneously.
BACKGROUND: Micro- and nanoplastics (MNPs) and homosalate (HMS) are ubiquitous emerging environmental contaminants detected in human samples. Despite the well-established endocrine-disrupting effects (EDEs) of HMS, the interaction between MNPs and HMS and its impact on HMS-induced EDEs remain unclear. OBJECTIVES: This study aimed to investigate the influence of MNPs on HMS-induced estrogenic effects and elucidate the underlying mechanisms in vitro and in vivo. METHODS: We assessed the impact of polystyrene nanospheres (PNSs; [Formula: see text] , [Formula: see text]) on HMS-induced MCF-7 cell proliferation (HMS: [Formula: see text] , equivalent to [Formula: see text]) using the E-SCREEN assay and explored potential mechanisms through transcriptomics. Adult zebrafish were exposed to HMS ([Formula: see text]) with or without PNSs ([Formula: see text] , [Formula: see text]) for 21 d. EDEs were evaluated through gonadal histopathology, fertility tests, steroid hormone synthesis, and gene expression changes in the hypothalamus–pituitary–gonad–liver (HPGL) axis. RESULTS: Coexposure of HMS and PNSs resulted in higher expression of estrogen receptor [Formula: see text] (ESR1) and the mRNAs of target genes (pS2, AREG, and PGR), a greater estrogen-responsive element transactivation activity, and synergistic stimulation on MCF-7 cell proliferation. Knockdown of serum and glucocorticoid-regulated kinase 1 (SGK1) rescued the MCF-7 cell proliferation induced by PNSs alone or in combination with HMS. In zebrafish, coexposure showed higher expression of SGK1 and promoted ovary development but inhibited spermatogenesis. In addition, coexposure led to lower egg hatchability, higher embryonic mortality, and greater larval malformation. Coexposure also modulated steroid hormone synthesis genes (cyp17a2, hsd17 [Formula: see text] 1, esr2b, vtg1, and vtg2), and resulted in higher [Formula: see text] ([Formula: see text]) release in females. Conversely, males showed lower testosterone, [Formula: see text] , and gene expressions of cyp11a1, cyp11a2, cyp17a1, cyp17a2, and hsd17 [Formula: see text] 1. DISCUSSION: PNS exposure exacerbated HMS-induced estrogenic effects via SGK1 up-regulation in MCF-7 cells and disrupting the HPGL axis in zebrafish, with gender-specific patterns. This offers new mechanistic insights and health implications of MNP and contaminant coexposure. https://doi.org/10.1289/EHP13696
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