Bisphenol A glucuronide deconjugation is a determining factor of fetal exposure to bisphenol A. (January 2016)

• Record Type: Journal Article
• Authors: Gauderat, Glenn; Picard-Hagen, Nicole; Toutain, Pierre-Louis; Corbel, Tanguy; Viguié, Catherine; Puel, Sylvie; Lacroix, Marlène Z.; Mindeguia, Pierre; Bousquet-Melou, Alain; Gayrard, Véronique
• Is Part Of: Environment international. Volume 86(2016:Jan.)
• Page Start: 52
• Page End: 59
• Publication Date: 2016-01
• Subjects: Bisphenol A -- Bisphenol A glucuronide -- Hydrolysis -- Fetus -- Toxicokinetic; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2015.10.006
• Languages: English
• ISSNs: 0160-4120

Abstract

Abstract: Previous studies in experimental animals have shown that maternal exposure to bisphenol A (BPA) during late pregnancy leads to high plasma concentrations of BPA glucuronide (BPAG) in fetus compared to mother due to the inability of BPAG to cross the placental barrier. A recent in vitro study has reported that BPAG can exert adipogenic effect underlining the need for characterization of the fetal disposition of BPAG. Experiments were conducted in chronically catheterized fetal sheep to determine the contribution of BPAG hydrolysis to BPA to the elimination of BPAG from the fetal compartment and its resulting effect on the overall fetal exposure to free BPA. Serial sampling of fetal arterial blood, amniotic fluid, maternal venous blood and urine was performed following separate single doses of BPA and BPAG administered intravenously to eight fetal/maternal pairs after cesarean section, and repeated BPAG doses given to two fetal sheep. On average 67% of the BPA entering the fetal circulation was rapidly eliminated through fetal to maternal clearance, with a very short half-life (20 min), while the remaining fraction (24%) was glucuronoconjugated. BPA conjugation–deconjugation cycling was responsible for a 43% increase of the overall fetal exposure to free BPA. A very specific pattern of fetal exposure to free BPA was observed due to its highly increased persistence with a hydrolysis-dependent plasma terminal free BPA half-life of several tens of hours. These findings suggest that although the high fetal to maternal clearance of free BPA protects the fetus from transient increases in free BPA plasma concentrations associated with maternal BPA intake, low but sustained basal free BPA concentrations are maintained in the fetus through BPA conjugation–deconjugation cycling. The potential health implications of these low but sustained basal concentrations of free BPA in fetal plasma should be addressed especially when considering time-dependent effects. Graphical abstract: Highlights: Fetal sheep was used to evaluate BPA and BPAG toxicokinetic parameters. The fetal to maternal transfer and the extent of BPA conjugation were 70 and 30%. Fetal BPAG elimination involved hydrolysis. The hydrolysis of BPAG resulted in a highly increased persistence of fetal BPA.