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

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

Author information

1
Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Elche, Spain. Electronic address: jesteban@umh.es.
2
Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Elche, Spain.
3
Instituto de Biología Molecular y Celular (IBMC), Universidad Miguel Hernández de Elche, Elche, Spain; Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernández de Elche, Elche, Spain; Centro de Investigación Biomédica En Red de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Universidad Miguel Hernández de Elche, Elche, Spain.
4
Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Elche, Spain; Centro de Investigación Biomédica En Red de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Universidad Miguel Hernández de Elche, Elche, Spain.

Abstract

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

PMID:
30790712
DOI:
10.1016/j.fct.2019.02.023

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