Combined Effects of Polystyrene Nanosphere and Homosolate Exposures on Estrogenic End Points in MCF-7 Cells and Zebrafish.

Autor:	Rongyi Ye¹, Zhiming Li¹, Hongyi Xian¹, Yizhou Zhong¹, Boxuan Liang¹, Yuji Huang¹, Da Chen², Mingzhu Dai³, Shuqin Tang², Jie Guo³, Ruobing Bai¹, Yu Feng¹, Zhenguo Chen⁴, Xingfen Yang⁵, Zhenlie Huang¹ huangzhenlie858252@smu.edu.cn
Předmět:	Salicylates Fishes Pollution Animal experimentation *Endocrine disruptors In vitro studies Fertility Research funding Cell proliferation Estrogen In vivo studies Descriptive statistics Reverse transcriptase polymerase chain reaction Cell lines Gene expression Messenger RNA Genes Estrogen receptors Molecular structure Oxidoreductases Western immunoblotting Histological techniques Microplastics Genetic techniques Comparative studies Data analysis software Cell receptors Glucocorticoids
Zdroj:	Environmental Health Perspectives. Feb2024, Vol. 132 Issue 2, p027011-1-027011-20. 20p.
Abstrakt:	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; 50 nm, 1.0 mg/L) on HMS-induced MCF-7 cell proliferation (HMS: 0:01-1 μM, equivalent to 2.62-262 μg/L) using the E-SCREEN assay and explored potential mechanisms through transcriptomics. Adult zebrafish were exposed to HMS (0.0262-262 μg/L) with or without PNSs (50 nm, 1.0 mg/L) 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 α (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, hsd17β1, esr2b, vtg1, and vtg2), and resulted in higher 17β-estradiol (E2) release in females. Conversely, males showed lower testosterone, E2, and gene expressions of cyp11a1, cyp11a2, cyp17a1, cyp17a2, and hsd17β1. 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. [ABSTRACT FROM AUTHOR]
Databáze:	GreenFILE
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