Is reproductive toxicity of bisphenols an adverse outcome from insulin homeostasis disruption in fish?

Beyond regulating glucose metabolism and energy homeostasis, insulin dysregulation impairs mammalian fertility by disrupting hormone secretion, but its role in fish reproduction remains poorly characterized. Here, a transcriptome-based systematic review of 19 screened studies revealed that exposure to pollutants (bisphenols) caused dual changes in insulin signaling and reproductive processes across species, suggesting a potential mechanistic link. Bisphenols (BPs) are a typical class of endocrine-disrupting chemicals. Molecular docking assessed binding affinities of ten BPs to insulin and its receptor across species, with BPZ and BPM showing stronger affinities than BPA. Juvenile Chinese rare minnows (Gobiocypris rarus) were exposed to BPA, BPZ, or BPM (1-100 μg/L) for 60 days. The reproductive development including reduced gonadosomatic index, inhibited oogenesis, and enhanced spermatogenesis were impaired at all treatments. Moreover, insulin-related gene expression along the HPG axis was altered, accompanied by suppressed insulin and disrupted sex hormone levels. Spearman correlation analysis revealed strong correlations between insulin and HPG axis hormones in males (r = 0.41-0.90, p = 0.02-0.21) and fair correlations in females (r = 0.48-0.61, p = 0.11-0.23). Those findings indicated that bisphenols-induced reproductive toxicity maybe mediated by insulin homeostasis disruption.