Bisphenol analogue exposure at low concentrations modifies heart-brain functions and transcriptomics in zebrafish larvae

Abstract

Substituting bisphenol A (BPA) with analogues could mitigate environmental harm. By mimicking water contamination and using zebrafish larvae, we tested the hypothesis that low environmentally relevant concentrations of BPS, BPF, and BPAF, compared to BPA, elicit physiological and molecular modifications. We verified lethal doses (LD₅₀; BPAF > BPF > BPA > BPS) using an OECD-compliant protocol and reported the absence of morphological and muscle abnormalities, and hatching delays below the LD₅₀ at 5 days post-fertilization (dpf). We identified the lowest bisphenol exposure levels that provoke the most significant motor-swimming changes (100 ng/L BPS, 10 ng/L BPF, 100 ng/L BPAF, and 100 ng/L BPA). We asked whether the observed motor phenotype at low bisphenol levels could be underpinned by heart-brain electrophysiological adaptations. Using in vivo optical mapping, we found increased high-frequency, low-amplitude brain activity and, in the cases of BPF and BPAF, bradycardia. Within these specific low-exposure settings, transcriptomics identified eight genes involved in heart-brain functions, homeostatic and immune regulation, that were down-regulated by each bisphenol, namely anxa1c, vwa10.1, zgc:172053, grna.2, ehf, gna14, ca15c, atp1a1a.5. Low environmentally relevant concentrations of bisphenol analogues modify organ physiology and the transcriptome in zebrafish larvae. The implications for ecotoxicology and the one-health framework are discussed.

Keywords: Bisphenol analogues; Environmental levels; Heart-brain functions; Neurophysiology; Transcriptomics; Zebrafish larvae.