Reproductive toxicity of bisphenol A and nitro-bisphenol A in male zebrafish at environmentally relevant concentrations

Bisphenol A (BPA) is a well-known endocrine-disrupting pollutant that poses significant environmental challenges globally. However, the toxicity of nitro-BPA (NBPA), the primary transformation product of BPA, remains poorly understood. This study employs a multi-omics approach, integrating in silico and bioinformatics analyses, to investigate and compare the male reproductive toxicity of BPA and NBPA in male zebrafish exposed to environmentally relevant concentrations. After 21 days of exposure, we observed a significant increase in cumulative egg production over five days in the NBPA 200 nM group compared to pre-exposure levels. Conversely, the gonadosomatic index of NBPA 200 nM group was significantly reduced by approximately 41.65 %. Our findings indicate that the activation of ESRRγ and inhibition of NR5A2 are critical molecular initiating events linked to male reproductive toxicity. Additionally, both BPA and NBPA were found to disrupt several key events within the steroid hormone biosynthesis pathway. This disruption includes the downregulation of genes encoding cytochrome P450 (CYP450) and hydroxysteroid dehydrogenase enzymes, as well as alterations in the levels of steroid hormones such as cholesterol and 25-hydroxycholesterol. Our study identifies biomolecular targets of BPA and NBPA at environmentally relevant concentrations that induce reproductive toxicity, enhancing our understanding of NBPA toxicity and are anticipated to inform the development of effective mitigation strategies.