4.5 Article

The xenoestrogens, bisphenol A and para-nonylphenol, decrease the expression of the ABCG2 transporter protein in human term placental explant cultures

Journal

MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 429, Issue C, Pages 41-49

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2016.03.034

Keywords

Human placenta; BCRP; Diethylstilbestrol; Endocrine disruptors; Xenobiotic transporters; Estrogen receptors

Funding

  1. Finnish Graduate School of Toxicology within the FinPharmaNet, Thule Institute
  2. University of Oulu
  3. Oulu University Scholarship Foundation
  4. Yrjo Jahnsson Foundation
  5. Northern Finland Cancer Association
  6. EU network: NewGeneris [FOOD-CT-2005 016320]
  7. EU network: ReProTect [LSHB-CT-2004-503257]
  8. EU network: ArcRisk [FP7-ENV-2008-1]

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Many endogenous and xenobiotic compounds are substrates and regulators of human placental ABC transporters. ABCG2 is protecting fetus against foreign chemicals. Environmental xenoestrogens, like bisphenol A (BPA) and p-nonylphenol (p-NP), mimic natural estrogens and can affect hormonal systems. Effects of BPA, p-NP, DES (diethylstilbestrol) and estradiol (E2), on ABCG2 expression were studied using human first trimester and term placental explants. Role of estrogen receptors (ER) in the effects of chemicals was studied by ER antagonist. Term placenta expressed less ABCG2 protein. In term placentas BPA (p < 0.05), p-NP (p < 0.01) and E2 (p < 0.05) decreased the ABCG2 protein expression after 48 h exposure while after 24 h exposure, only E2 decreased the expression (p < 0.05). The chemicals did not affect ABCG2 in first trimester placentas. The ER antagonist affected differently the responses of chemicals. In conclusion, environmental xenoestrogens downregulate placental ABCG2 protein expression depending on gestational age. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

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