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Conjugation and deconjugation reactions within the fetoplacental compartment in a sheep model: a key factor determining bisphenol A fetal exposure
- Source :
- Drug Metabolism and Disposition, Drug Metabolism and Disposition, American Society for Pharmacology and Experimental Therapeutics (ASPET), 2015, 43 (4), pp.467-76. ⟨10.1124/dmd.114.061291⟩
- Publication Year :
- 2015
-
Abstract
- International audience; The widespread human exposure to bisphenol A (BPA), an endocrine disruptor targeting developmental processes, underlines the need to better understand the mechanisms of fetal exposure. Animal studies have shown that at a late stage of pregnancy BPA is efficiently conjugated by the fetoplacental unit, mainly into BPA-glucuronide (BPA-G), which remains trapped within the fetoplacental unit. Fetal exposure to BPA-G might in turn contribute to in situ exposure to bioactive BPA, following its deconjugation into parent BPA at the level of fetal sensitive tissues. The objectives of our study were 1) to characterize the BPA glucurono- and sulfoconjugation capabilities of the ovine fetal liver at different developmental stages, 2) to compare hepatic conjugation activities in human and sheep, and 3) to evaluate the extent of BPA conjugation and deconjugation processes in placenta and fetal gonads. At an early stage of pregnancy, and despite functional sulfoconjugation activity, ovine fetuses expressed low hepatic BPA conjugation capabilities, suggesting that this stage of development represents a critical window in terms of BPA exposure. Conversely, the late ovine fetus expressed an efficient detoxification system that metabolized BPA into BPA-G. Hepatic glucuronidation activities were quantitatively similar in adult sheep and humans. In placenta, BPA conjugation and BPA-G deconjugation activities were relatively balanced, whereas BPA-G hydrolysis was systematically higher than BPA conjugation in gonads. The possible reactivation of BPA-G into BPA could contribute to an increased exposure of fetal sensitive tissues to bioactive BPA in situ.
- Subjects :
- Male
endocrine system
medicine.medical_specialty
Bisphenol A
[SDV]Life Sciences [q-bio]
Placenta
Glucuronidation
Pharmaceutical Science
Gestational Age
010501 environmental sciences
Biology
Endocrine Disruptors
In Vitro Techniques
01 natural sciences
Models, Biological
03 medical and health sciences
chemistry.chemical_compound
Fetus
Glucuronides
Phenols
Species Specificity
Pregnancy
Internal medicine
Detoxification
medicine
Animals
Humans
Benzhydryl Compounds
Maternal-Fetal Exchange
030304 developmental biology
0105 earth and related environmental sciences
Pharmacology
0303 health sciences
Sheep
urogenital system
medicine.disease
Endocrinology
medicine.anatomical_structure
chemistry
Endocrine disruptor
Liver
Data Interpretation, Statistical
Female
Animal studies
hormones, hormone substitutes, and hormone antagonists
Subcellular Fractions
Subjects
Details
- ISSN :
- 1521009X and 00909556
- Volume :
- 43
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Drug metabolism and disposition: the biological fate of chemicals
- Accession number :
- edsair.doi.dedup.....b384f4b0b6662853d180a4bfae760148