6PPD and 6PPD Quinone Induce Endometrial Cell Dysfunction via Activating ERα and GPER at Human-Relevant Levels DOI
Lei Tang, Xin Li, Shengtao Zhu

et al.

Environmental Science & Technology, Journal Year: 2025, Volume and Issue: unknown

Published: May 14, 2025

The widespread environmental prevalence of tire-derived N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and 6PPD-quinone (6PPD-Q) has provoked public concern about their health risks. This study aimed to investigate the potential 6PPD 6PPD-Q induce endometrial cell dysfunction through nuclear estrogen receptor (ER) G-protein-coupled (GPER) signaling pathways. Fluorescence competitive binding reporter gene assays revealed that selectively bound ERα (not ERβ) activated ER transcriptional activity, with lowest observed effective concentrations (LOECs) 500 10 nM, respectively. Calcium mobilization further demonstrated both GPER nongenomic pathway in a concentration-dependent manner (LOEC = 1 nM). exhibited stronger activation potency than 6PPD, which was explained well by molecular dynamics simulation. stimulated proliferation via ERα/GPER pathways, mechanistically linked Cyclin D1/Ki67 upregulation. Furthermore, 6PPD/6PPD-Q promoted migration an ERα/GPER-regulated epithelial-mesenchymal transition inflammatory responses. Notably, LOECs for these functional disruptions reached nanomolar levels relevant human exposure. Collectively, we elucidated initial events downstream key 6PPD/6PPD-Q-induced dysfunction, implied threat reproductive system provided novel perspectives risk evaluation.

Language: Английский

Associations between phenol and paraben exposure and the risk of developing breast cancer in adult women: a cross-sectional study DOI Creative Commons
Yao Xiong, Zhiyu Li, Xiong Xiong

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 3, 2025

Increasing evidence suggests that endocrine-disrupting chemicals (EDCs) have adverse effects on breast cancer (BC). The aim of this study was to assess the association between exposure prevalent EDCs—phenols and parabens—and risk developing BC. Data urinary bisphenol A (BPA), triclosan (TRS), benzophenone-3 (BP3), methyl paraben (MPB), ethyl (EPB), propyl (PPB), butyl (BUP) were obtained from 2005–2014 National Health Nutrition Examination Survey. total 4455 subjects included in cross-sectional study. results weighted multivariable regression models indicated elevated concentrations TRS increased BC by 2.33 (Q2: 95% CI = 1.45–3.75, p < 0.001) 1.94 times (Q3: 1.21–3.09, 0.006), respectively. nonlinear statistically significant (P 0.007), with restricted cubic splines (RCS) curve exhibiting an inverted U shape. more pronounced among overweight individuals (BMI ≥ 25 kg/m2), those aged 60 years, white individuals. Weighted quantile sum (WQS) Bayesian Kernel Machine Regression (BKMR) analysis revealed no overall mixtures phenol metabolites risk. However, most influential, higher (both continuous categorical) significantly associated risk, particularly

Language: Английский

Citations

1
The intestinal toxicity mechanisms of Triclosan and Triclocarban and their possible clinical nutritional intervention mechanisms DOI
Xinyu Fang, Jinfeng Zhao, Simin Wu

et al.

Environmental Pollution, Journal Year: 2025, Volume and Issue: unknown, P. 126396 - 126396

Published: May 1, 2025

Language: Английский

Citations

0
6PPD and 6PPD Quinone Induce Endometrial Cell Dysfunction via Activating ERα and GPER at Human-Relevant Levels DOI
Lei Tang, Xin Li, Shengtao Zhu

et al.

Environmental Science & Technology, Journal Year: 2025, Volume and Issue: unknown

Published: May 14, 2025

The widespread environmental prevalence of tire-derived N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and 6PPD-quinone (6PPD-Q) has provoked public concern about their health risks. This study aimed to investigate the potential 6PPD 6PPD-Q induce endometrial cell dysfunction through nuclear estrogen receptor (ER) G-protein-coupled (GPER) signaling pathways. Fluorescence competitive binding reporter gene assays revealed that selectively bound ERα (not ERβ) activated ER transcriptional activity, with lowest observed effective concentrations (LOECs) 500 10 nM, respectively. Calcium mobilization further demonstrated both GPER nongenomic pathway in a concentration-dependent manner (LOEC = 1 nM). exhibited stronger activation potency than 6PPD, which was explained well by molecular dynamics simulation. stimulated proliferation via ERα/GPER pathways, mechanistically linked Cyclin D1/Ki67 upregulation. Furthermore, 6PPD/6PPD-Q promoted migration an ERα/GPER-regulated epithelial-mesenchymal transition inflammatory responses. Notably, LOECs for these functional disruptions reached nanomolar levels relevant human exposure. Collectively, we elucidated initial events downstream key 6PPD/6PPD-Q-induced dysfunction, implied threat reproductive system provided novel perspectives risk evaluation.

Language: Английский

Citations

0