Work

Bisphenol A exposure impairs cardiometabolic health: Integrative human evidence and zebrafish heart multi-omics analysis

Year: 2026

Type: article

Abstract: OBJECTIVE: Bisphenol A (BPA) is a widely used endocrine-disrupting chemical potentially linked to cardiometabolic disorders. However, the association between BPA exposure and cardiometabolic index (CMI), as well as the underlying cardiac molecular mechanisms, remains insufficiently understood. This study aimed to investigate the associations between BPA exposure and CMI in humans, and to explore direct cardiac effects and underlying molecular mechanisms in a zebrafish model. METHODS: Data from 844 participants in the NHANES survey were analyzed to assess associations between BPA and CMI, including stratified analyses and mediation analyses of inflammatory biomarkers. In parallel, zebrafish were exposed to BPA, and cardiac injury was evaluated using histopathology, RNA sequencing, and untargeted metabolomics. RESULTS: In NHANES, BPA was positively associated with CMI (β = 0.12, 95% CI: 0.00-0.25, P = 0.049). The association was stronger in participants aged 21-39 years (β = 0.17, 95% CI: 0.06-0.27, P = 0.009) and in non-Hispanic Whites (β = 0.14, 95% CI: 0.01-0.26, P = 0.033). Mediation analysis indicated that C-reactive protein accounted for 30.11% and albumin for 11.79% of the total effect. In zebrafish, BPA exposure induced cardiac histopathological abnormalities, including disorganized myocardial fibers and inflammatory infiltration, without gross morphological changes. RNA-seq identified 380 differentially expressed genes, which were enriched in metabolic, signaling, and immune pathways. Metabolomics revealed 83 altered metabolites after annotation from combined positive and negative ionization modes, with downregulation of 5-HETE and upregulation of steroid- and terpenoid-related metabolites, indicating disruption of lipid mediator and steroid metabolism. CONCLUSIONS: BPA exposure is associated with elevated CMI in humans, with partial mediation by systemic inflammation. In zebrafish, BPA directly induces cardiac transcriptional and metabolic reprogramming, particularly affecting lipid and steroid pathways. These findings provide mechanistic insights into the link between BPA and cardiometabolic risk.

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2026.120037

Authors: Xiangbin Liu, Jun Yi, Zhenyu Li

Institutions: Central South University, Third Xiangya Hospital, Xiangya Hospital Central South University

Language: English

Topic: Effects and risks of endocrine disrupting chemicals

Subfield: Health, Toxicology and Mutagenesis

Field: Environmental Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,650