Integrated transcriptome analysis of rats exposed to bisphenol mixtures from the fetal to developmental stage

Bisphenol A (BPA), widely used in plastics and resins, has raised health concerns for its endocrine-disrupting effects. BPA analogues such as bisphenol S (BPS) and bisphenol F (BPF) emerged as alternatives but exhibit similar risks. Despite regulations on BPA in many countries, alternatives remain insufficiently controlled. Although the safety of BPS and BPF has not been sufficiently verified, these compounds have already been detected in various environmental sources and human urine, raising serious concerns. While bisphenols are expected to have various adverse effects, research remains limited. This study investigates the adverse effects of bisphenols mixture on rats from fetal stage to young adulthood by analyzing transcriptomes in multiple tissues-liver, kidney, thyroid gland, and reproductive organs-and by gender, to identify key genes affected by bisphenol exposure. Dams were orally administered test substances from gestational day 6 to lactation day 6, and F1 pups received the same substances at half the concentration from postnatal day 7 to day 63. Transcriptome analysis of the collected tissues identified core genes related to high-density lipoprotein metabolism and hormone secretion, providing insights into mechanisms through which BPA may disrupt hormonal balance. Furthermore, the study suggests that combined exposure to BPA, BPS, and BPF produces distinct effects compared to BPA alone, with pronounced impacts on the thyroid and reproductive organs, despite individual concentrations being below the no-observed-adverse-effect-level. These findings highlight the potential cumulative impact of endocrine disrupting chemicals in the body.