In utero exposure to bisphenol-A disrupts key elements of retinoid system in male mice offspring

Food Chem Toxicol. 2019 Apr;126:142-151. doi: 10.1016/j.fct.2019.02.023. Epub 2019 Feb 18.


The retinoid system controls essential cellular processes including mitosis, differentiation and metabolism among others. Although the retinoid-signalling pathway is a potential target for the action of several endocrine disrupting chemicals (EDCs), the information about the developmental effects of bisphenol-A (BPA) on the hepatic retinoid system is scarce. Herein, male mice were in utero exposed to BPA following maternal subcutaneous doses of 0, 10 and 100 μg/kg bw/day from gestational day 9-16 and they were sacrificed at post-natal day 30. Retinoid concentrations and gene expression of key elements involved in the retinoid system were determined in liver. BPA increased all-trans-retinoic acid concentration and expression of Adh1, Aox1 and Cyp1a2 (biosynthesis of retinoic acid), while reduced Mrp3 (efflux from hepatocyte to blood), increased Bcrp expression (biliary excretion) and changed the retinoid-dependent signalling system after reducing expression of Rxrβ and increasing that of Fgf21. Furthermore, we found bivariate associations of Rarγ and Rxrγ expressions with all-trans-retinoic acid concentrations and of Fgf21 expression with that of Rarγ. Those findings occurred in animals which showed altered pancreatic function and impaired glucose metabolism during adulthood. The present information should be useful for enhancing testing methods for the identification of EDCs.

Keywords: All-trans-retinoic acid; Bisphenol-A; Endocrine disruption; Fibroblast growth factor 21; Retinoid system.

MeSH terms

  • Animals
  • Benzhydryl Compounds / adverse effects*
  • Endocrine Disruptors / adverse effects*
  • Female
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Maternal Exposure / adverse effects*
  • Mice
  • Phenols / adverse effects*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / etiology*
  • Prenatal Exposure Delayed Effects / genetics
  • Prenatal Exposure Delayed Effects / metabolism
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism
  • Retinoids / metabolism*
  • Uterus / drug effects
  • Uterus / metabolism


  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Phenols
  • Receptors, Retinoic Acid
  • Retinoids
  • fibroblast growth factor 21
  • retinoic acid receptor gamma
  • Fibroblast Growth Factors
  • bisphenol A