Placental transfer of conjugated bisphenol A and subsequent reactivation in the rat fetus.
Open accessAbstract
Background: Bisphenol A (BPA), a well-known endocrine disruptor, is highly glucuronidated in the liver, and the resultant BPA-glucuronide (BPA-GA) is excreted primarily into bile. However, in rodents, prenatal exposure to low doses of BPA can adversely affect the fetus, despite the efficient drug-metabolizing systems of the dams. The transport mechanisms of BPA from mother to fetus are unknown. Objectives: To test our hypothesis that BPA-GA—an inactive metabolite—is passed through the placenta to the fetus, where it affects the fetus after reactivation, we investigated the placental transfer of BPA-GA and reactivation to BPA in the fetus. Methods: After performing uterine perfusion with BPA-GA in pregnant rats, we examined the expression and localization of the placental transporters for drug metabolites in the perfusate by reverse-transcriptase polymerase chain reaction and immunohistochemistry. We also investigated the deconjugation of BPA-GA in the fetus and examined uridine 5′-diphospho-glucuronosyltransferase (UGT) activity toward BPA and the expression of UGT isoforms in fetal liver. Results: We detected BPA-GA and deconjugated BPA in the fetus and amniotic fluid after perfusion. In the trophoblast cells, organic anion-transporting polypeptide 4a1 (Oatp4a1) was localized on the apical membrane, and multidrug resistance-associated protein 1 (Mrp1) was localized to the basolateral membrane. We observed deconjugation of BPA-GA in the fetus; furthermore, we found the expression of UGT2B1, which metabolizes BPA, to be quite low in the fetus. Conclusions: These results demonstrate that BPA-GA is transferred into the fetus and deconjugated in the fetus because of its vulnerable drug-metabolizing system.
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BPA readily crosses the placenta, exposing fetal tissues to concentrations close to those in maternal placenta.
“BPA readily crosses the placenta [46], [47], exposing fetal tissues to concentrations close to those in maternal placenta [48].”
From Gestational Exposure to Low Dose Bisphenol A Alters Social Behavior in Juvenile Mice (2011) · cites this paper as [47]
The Results and Discussion (page unavailable) report that BPA-glucuronide crossed the placenta in pregnant rats and that small amounts of it and deconjugated BPA were detected in fetal tissues. They do not report fetal-tissue concentrations close to those in the maternal placenta; the Discussion instead describes the transfer as small. Thus, the source supports fetal exposure but not the concentration comparison attached to [48]. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn its inactive conjugated form, BPA can be unconjugated and re-activated in the fetus.
“Furthermore, in its inactivate conjugated form, BPA, can be unconjugated and re-activated in the fetus [47].”
From Gestational Exposure to Low Dose Bisphenol A Alters Social Behavior in Juvenile Mice (2011) · cites this paper as [47]
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Gestational Exposure to Low Dose Bisphenol A Alters Social Behavior in Juvenile Mice
Wolstenholme, J. T., Taylor, J. A., Shetty, S. R. J., Edwards, M., Connelly, J. J., & Rissman, E. F. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025448 · Cited by 168 · see citing works
“BPA readily crosses the placenta [46,47], exposing fetal tissues to concentrations close to those in”
BackgroundCao, X.-L., Zhang, J., Goodyer, C. G., Hayward, S., Cooke, G. M., & Curran, I. H. A. (2012) · Chemosphere · doi:10.1016/j.chemosphere.2012.05.003 · Cited by 93 · see citing works
Thongkorn, S., Kanlayaprasit, S., Jindatip, D., Tencomnao, T., Hu, V. W., & Sarachana, T. (2019) · Scientific Reports · doi:10.1038/s41598-019-39386-w · Cited by 66 · see citing works
Barrett, E. S., Sathyanarayana, S., Mbowe, O., Thurston, S. W., Redmon, J. B., Nguyen, R. H. N., & Swan, S. H. (2017) · Environmental Health Perspectives · doi:10.1289/ehp875 · Cited by 65 · see citing works
- Authors
- Nishikawa, M., Iwano, H., Yanagisawa, R., Koike, N., Inoue, H., & Yokota, H.
- Affiliations
- Laboratory of Veterinary Biochemistry, Department of Bioscience, School of Veterinary Medicine and
- Rakuno Gakuen University (JP)
- Corresponding author
- Iwano, Hidetomo
- Venue
- Environmental Health Perspectives
- Publisher
- American Chemical Society (ACS)
- Published
- 2010-04-09
- Volume
- 118
- Issue
- 9
- Pages
- 1196-1203
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- PMC
- PMC2944077
- OpenAlex
- W2056456647
- Cited by
- 229
- References
- 0
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 19 · 2023: 13 · 2022: 13 · 2021: 22 · 2020: 19 · 2019: 11 · 2018: 11 · 2017: 13 · 2016: 21 · 2015: 18 · 2014: 8 · 2013: 12 · 2012: 15
- FWCI
- 10.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- creativecommons.org/licenses/by/4.0/ (vor, 2821 d)
- Locations
- Environmental Health Perspectives (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Keywords
- bisphenol A, BPA glucuronide, placental transfer, deconjugation, UGT2B1, MRP1, trophoblast, endocrine disruptors, prenatal exposure, amniotic fluid, rat fetus
- MeSH terms
- Bisphenol A Compounds, Amniotic Fluid, Animals, Benzhydryl Compounds, Chromatography, High Pressure Liquid, Female, Fetus, Immunohistochemistry, Phenols, Placenta, Pregnancy, Mass Spectrometry, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Glucuronides, Rats
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