The increasing global use of organophosphate esters (OPEs) has raised concerns about their environmental and health impacts, with evidence suggesting adverse effects on reproductive system health. As a widely used OPE, triphenyl phosphate (TPHP) has drawn attention for its endocrine-disrupting properties; however, its effects on cervical epithelial cells and association with cervical diseases remain unclear. In this study, analysis of 12 urinary OPE metabolites (mOPEs) in 116 cervical cancer (CC) cases and 116 controls revealed that multiple exposure biomarkers, particularly those related to TPHP exposure, were significantly positively associated with CC risk, suggesting a potential link between OPE exposure and disease development. In toxicological experiments, acute exposure to TPHP (50 μM, 24 h) induced significant cytotoxicity in human cervical epithelial cells (HcerEpic), characterized by reduced cell viability, cell cycle disruption, apoptosis, and oxidative stress. Conversely, chronic low-dose exposure (100 nM, 30 weeks) conferred a survival advantage to HcerEpic cells and enhanced their epithelial-mesenchymal transition (EMT) capacity, with enhanced tumor formation ability observed in a nude mouse xenograft model. Transcriptomic analysis revealed that ferroptosis was a significantly enriched pathway in both exposure models. Furthermore, experimental validation confirmed that acute TPHP exposure induced ferroptosis in HcerEpic cells, whereas chronically exposed cells exhibited ferroptosis resistance. Collectively, our findings highlight the critical role of ferroptosis dysregulation in TPHP-induced acute and chronic toxicities in HcerEpic cells, suggesting that TPHP may be a potential risk factor for CC and underscoring the need for further attention to the health risks associated with OPE exposure.
Yamei Nie, Shizhi Wang, Wei Sun et al.· Journal of Applied Toxicolog...· 0 citations
BACKGROUND
Studies have indicated that exposure to household pesticides is prevalent among the population. Nevertheless, the relationship and contributing factors linking urinary metabolites of household pesticides to circulating levels of sex steroid hormones in human serum remain insufficiently explored.
OBJECTIVE
To examine the correlation between household pesticides metabolites and serum sex steroid hormones levels.
METHODS
This study utilized data from 3,884 participants obtained through the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. NHANES measured urinary metabolites of household pesticides and serum levels of sex steroid hormones. The study utilized weighted multiple linear regression modeling combined with restricted cubic spline (RCS) analysis to investigate relationships and dose-response patterns between residential pesticide metabolites and serum sex steroid hormones across both genders. Additionally, the research examined potential modifying effects of obesity status on pesticide metabolite-sex hormone associations through interaction analysis.
RESULTS
Following adjustment for potential confounders, concentrations of 3,5,6-trichloro-2-pyridinol (TCPY), para-nitrophenol (PNP), and 3-phenoxybenzoic acid (3-PBA) demonstrated negative correlations with total serum testosterone (TT), estradiol concentrations(E2), and free androgen index (FAI) across all three statistical models (Ps < 0.05), while positive relationships emerged with sex hormone-binding globulin (SHBG). We found the similar results among male participants. However, the negative correlation was not found between TCPY, PNP, 3-PBA and SHBG among female participants RCS modeling revealed complex nonlinear interactions between DCBA and serum sex steroid hormone levels. Analysis stratified by body mass index showed that TCPY, PNP and 3-PBA exhibited similar negative correlations with TT, E2 and FAI in the non-obese participants.
CONCLUSIONS
The study reveals that the metabolites from household pesticides exhibited negative correlations with serum sex steroid hormone levels across both genders. Associations were more consistent for non-obese populations.
Yun Zheng, Shizhi Wang, Haohan Liu et al.· Reproductive Toxicology· 0 citations
