Exploring the Reproductive Toxicity of Bisphenol S Through a Network Toxicology and Molecular Docking Analysis

ABSTRACT The aim of this study was to investigate the potential reproductive toxicity of bisphenol S (BPS) and the related molecular mechanisms through a network toxicology approach. By utilizing various databases, including the Comparative Toxicogenomics Database (CTD), GeneCards, Online Mendelian Inheritance in Man (OMIM), the Pharmacogenomics Knowledgebase (PharmGKB), and the Therapeutics Target Database (TTD), and limiting the species to Homo sapiens , we confirmed 45 potential targets related to both BPS exposure and reproductive injury. Additional analysis via STRING and Cytoscape pinpointed 4 key targets: AKT serine/threonine kinase 1 (AKT1), interleukin‐6 (IL‐6), interleukin‐1‐beta (IL‐1β), and tumor necrosis factor α (TNFα). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that the principal targets of BPS‐mediated reproductive damage are mainly involved in oxidative stress signaling and cell secretion pathways. Because PI3K/AKT regulates the secretion of IL‐6, IL‐1β, and TNFα, we focus on AKT1 in the molecular docking experiments. Unexpectedly, we found a strong interaction between BPS and AKT1. Furthermore, the results suggested that women may be more susceptible to BPS‐mediated reproductive toxicity than men. This study provides a theoretical framework for understanding the molecular mechanisms through which BPS causes reproductive toxicity and lays the foundation for preventing and treating reproductive disorders related to BPS exposure. In addition, our network toxicology‐based method can accelerate the discovery of pathways involved in the toxic effects of environmental chemicals that are currently unknown.