Integrated transcriptome analysis of rats exposed to bisphenol mixtures from fetus to developmental stage
Bisphenol A (BPA), widely used in plastics and resins, raised health concerns for its endocrine-disrupting effects. BPA analogues like bisphenol S (BPS) and bisphenol F (BPF) emerged as alternatives but were found to exhibit similar risks. Despite many countries have implemented BPA regulations, alternatives remain insufficiently regulated Although the safety of BPS and BPF has not been sufficiently verified, they have already been detected in various surrounding environments and human urine, raising serious concerns Bisphenols are expected to have various adverse effects, but research on this is lacking. This study explores the adverse effects of bisphenol mixtures on rats from fetus to young adulthood, analyzing transcriptomes by tissue and gender to identify key genes impacted by bisphenol exposure. Dams were orally administered test substances from gestational day 6 to lactation day 6. F1 pups received the same substances at half the concentration from postnatal day 7 to day 63. The tissues collected from the pups were subjected to transcriptome analysis, and core genes were identified through integrated analysis. The study identifies core genes associated with high-density lipoprotein and hormone secretion. These genes provide insights into the mechanisms through which BPA may cause hormonal imbalances. Furthermore, the study suggests that a complex exposure of BPA, BPS, and BPF can exerts different effects than BPA alone, pronounced effects on the thyroid and reproductive organs, even though individual concentrations were below the no-observed-adverse-effect-level. It highlights the potential cumulative impact of endocrine disrupting chemicals in the body. Overall design: The dose of a single bisphenol (Single) was selected as BPA 500 mg/kg/day and bisphenol mixture (Mix) was made at 500 mg/kg/day proportionally combined each of the three chemicals (BPA, 160 mg/kg/day; BPF, 160 mg/kg/day; BPS, 180 mg/kg/day). The pregnant SD rat assigned to 3 groups (VC, Single and Mix) were orally administered each test substance from gestational day 6 to lactation day 6. On postnatal day (PND) 4, F1 pups were culled to three male and female per F0 dam. F1 pups were orally administered the same test substance as F0 dam at half the concentration (250 mg/kg/day) from PND 7 to PND 63. For transcriptome analysis, pups were humanely sacrificed, and liver, kidney, thyroid, and reproductive organs including testis and ovary were collected.