Bisphenol A glucuronide deconjugation is a determining factor of fetal exposure to bisphenol A

Gauderat, Glenn; Picard‐Hagen, Nicole; Toutain, Pierre‐Louis; Corbel, Tanguy; Viguié, Catherine; Puel, Sylvie; Lacroix, Marlène Z.; Mindeguia, Pierre; Bousquet‐mélou, Alain; Gayrard, Véronique

doi:10.1016/j.envint.2015.10.006

Cited by 57 publications

(34 citation statements)

References 18 publications

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“…As previously mentioned, although many of these transporters show preference for sulfated conjugates, they are also capable of transporting (Gauderat et al, 2016), and to a greater extent than BPA-sulfate (Corbel et al, 2013(Corbel et al, , 2015. The authors also showed that microsomes and cytosols prepared from both fetal ewe and human livers have similar activity toward BPA glucuronidation and sulfation, respectively (Corbel et al, 2015).…”

Section: Resultssupporting

confidence: 49%

“…Interestingly, it has been shown that BPA-glucuronide is transported across the placenta to the rat fetus, where it can be deconjugated and thereby reactivated (Nishikawa et al, 2010). Similarly, it has been shown in sheep that the fetoplacental unit retains conjugated BPA metabolites (Corbel et al, 2013), creating a higher exposure of the fetus to bioactive BPA through conjugation-deconjugation cycling (Corbel et al, 2015;Gauderat et al, 2016). We have demonstrated that human fetal livers exhibit a wide range of quantifiable concentrations of both free and conjugated BPA, whereas levels in adult livers were typically below the limit of quantification (LOQ) (Nahar et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Correlation between Conjugated Bisphenol A Concentrations and Efflux Transporter Expression in Human Fetal Livers

Moscovitz

Nahar

Shalat

et al. 2016

Drug Metabolism and Disposition

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Because of its widespread use in the manufacturing of consumer products over several decades, human exposure to bisphenol A (BPA) has been pervasive. Fetuses are particularly sensitive to BPA exposure, with a number of negative developmental and reproductive outcomes observed in rodent perinatal models. Xenobiotic transporters are one mechanism to extrude conjugated and unconjugated BPA from the liver. In this study, the mRNA expression of xenobiotic transporters and relationships with total, conjugated, and free BPA levels were explored utilizing human fetal liver samples. The mRNA expression of breast cancer resistance protein (BCRP) and multidrug resistance-associated transporter (MRP)4, as well as BCRP and multidrug resistance transporter 1 exhibited the highest degree of correlation, with r 2 values of 0.941 and 0.816 (P < 0.001 for both), respectively.Increasing concentrations of conjugated BPA significantly correlated with high expression of MRP1 (P < 0.001), MRP2 (P < 0.05), and MRP3 (P < 0.05) transporters, in addition to the NF-E2-related factor 2 transcription factor (P < 0.001) and its prototypical target gene, NAD(P)H quinone oxidoreductase 1 (P < 0.001). These data demonstrate that xenobiotic transporters may be coordinately expressed in the human fetal liver. This is also the first report of a relationship between environmentally relevant fetal BPA levels and differences in the expression of transporters that can excrete the parent compound and its metabolites. IntroductionBisphenol A (BPA) is an endocrine-disrupting chemical used in the manufacturing of plastics and epoxy resins and is incorporated into a variety of consumer products, including food packaging, children's toys, plastic containers, and medical supplies. There are multiple routes of human exposure to BPA. Leaching of BPA from consumer products has been shown to contaminate food, water, air, and dust (Vandenberg et al., 2007). BPA was investigated for use as a commercial, synthetic estrogen, although it was found to have a significantly weaker potency than diethylstilbestrol (Dodds and Lawson, 1936). Because of widespread use of BPA and its endocrine-disrupting properties, there has been ongoing attention placed on the potential for BPA to negatively affect human health (Ramakrishnan et al., 2009).Pregnant women and their offspring have been identified as potentially sensitive populations to a number of environmental endocrinedisrupting chemicals, including BPA (reviewed in Rubin, 2011).Biomonitoring studies have detected at least one form of BPA not only in the serum of pregnant women but also in a multitude of reproductive tissues, including cord blood, placenta, and amniotic fluid (Vandenberg et al., 2010), and fetal tissues such as the liver (Zhang et al., 2011;Cao et al., 2012;Nahar et al., 2013). Numerous studies conducted in rodents have associated negative outcomes with in utero exposure to BPA, including alterations to reproductive, neurologic, behavioral, and metabolic development (reviewed in Rubin, 2011). It has b...

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Section: Resultssupporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Correlation between Conjugated Bisphenol A Concentrations and Efflux Transporter Expression in Human Fetal Livers

Moscovitz

Nahar

Shalat

et al. 2016

Drug Metabolism and Disposition

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“…Specifically, exposures to BPA, DDT, PBDE, PCB and phthalates are highlighted. As noted above with respect to toxic metals, all of the endocrine disruptors discussed here are known to cross the placental barrier [71][72][73][74]. The studies detailed below are summarized in Supplementary Table 2. Bisphenol-A BPA, an industrial compound with significant estrogenic effects, is used in a variety of products as a component of polycarbonate plastics or epoxy resins [75].…”

Section: Endocrine Disruptorsmentioning

confidence: 99%

“…It has been posited that 'free' BPA is able to cross the placenta, while glucuronidated BPA cannot. Thus, the maternal capacity for clearance depends on the maternal clearance of BPA as well as the fetal capacity for conjugation, which may 'trap' glucuronidated BPA in the fetal compartment and prolong fetal exposure [71]. In a study that focused on the assessment of BPA exposure and effects in fetal tissue, fetal liver tissue was analyzed from the Washington Birth Defects Research Laboratory Fetal Biobank.…”

Section: Endocrine Disruptorsmentioning

confidence: 99%

Effects of Prenatal Exposure to Endocrine Disruptors and Toxic Metals on The Fetal Epigenome

2017

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Exposure to environmental contaminants during pregnancy has been linked to adverse outcomes at birth and later in life. The link between prenatal exposures and latent health outcomes suggests that these exposures may result in long-term epigenetic reprogramming. Toxic metals and endocrine disruptors are two major classes of contaminants that are ubiquitously present in the environment and represent threats to human health. In this review, we present evidence that prenatal exposures to these contaminants result in fetal epigenomic changes, including altered global DNA methylation, gene-specific CpG methylation and microRNA expression. Importantly, these changes may have functional cellular consequences, impacting health outcomes later in life. Therefore, these epigenetic changes represent a critical mechanism that warrants further study.

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“…BPA could be transported in both maternal-foetal and foetalmaternal direction over a BeWo monolayer, but with higher permeability in the foetal-maternal direction. The foetal to maternal clearance was investigated in toxicokinetic studies in sheep showing that about 70% of the BPA entering the foetal circulation (5 mg/kg) was rapidly removed by clearance of free BPA to the maternal circulation with a half-life of 20 min [118]. However, about a quarter of the 30 Adjusted for age, BMI, nationality, alcohol intake and history of chemical exposure.…”

Section: Foetal Exposure: Programming and Epigeneticsmentioning

confidence: 99%

New EU criteria for endocrine disrupters

2018

TemaNord

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Bisphenol A glucuronide deconjugation is a determining factor of fetal exposure to bisphenol A

Cited by 57 publications

References 18 publications

Correlation between Conjugated Bisphenol A Concentrations and Efflux Transporter Expression in Human Fetal Livers

Correlation between Conjugated Bisphenol A Concentrations and Efflux Transporter Expression in Human Fetal Livers

Effects of Prenatal Exposure to Endocrine Disruptors and Toxic Metals on The Fetal Epigenome

New EU criteria for endocrine disrupters

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