title: The xenoestrogens, bisphenol A and para-nonylphenol, decrease the expression of the ABCG2 transporter protein in human term placental explant cultures.
abstract: 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.
authors.affiliation: Research Unit of Biomedicine, Pharmacology and Toxicology, University of Oulu, P.O. Box 5000, 90014, University of Oulu, Oulu, Finland; Centre for Arctic Medicine, Thule Institute, University of Oulu, P.O. Box 7300, 90014, University of Oulu, Oulu, Finland. Electronic address: elina.sieppi@oulu.fi.
authors.forename: E
authors.initials: E
authors.lastname: Sieppi
authors.affiliation: Faculty of Health Sciences, School of Pharmacy/Toxicology, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland. Electronic address: kirsi.vahakangas@uef.fi.
authors.forename: K
authors.initials: K
authors.lastname: Vähäkangas
authors.affiliation: Centre for Arctic Medicine, Thule Institute, University of Oulu, P.O. Box 7300, 90014, University of Oulu, Oulu, Finland. Electronic address: arja.rautio@oulu.fi.
authors.forename: A
authors.initials: A
authors.lastname: Rautio
authors.affiliation: Department of Life Sciences, University of Siena, Via Aldo Moro 2, 53100, Siena, Italy. Electronic address: ietta@unisi.it.
authors.forename: F
authors.initials: F
authors.lastname: Ietta
authors.affiliation: Department of Life Sciences, University of Siena, Via Aldo Moro 2, 53100, Siena, Italy. Electronic address: luana.riccipaulesu@unisi.it.
authors.forename: L
authors.initials: L
authors.lastname: Paulesu
authors.affiliation: Centre for Arctic Medicine, Thule Institute, University of Oulu, P.O. Box 7300, 90014, University of Oulu, Oulu, Finland; Nordlab Oulu, P.O. Box 500, 90029, OYS, Oulu, Finland. Electronic address: paivi.myllynen@oulu.fi.
authors.forename: P
authors.initials: P
authors.lastname: Myllynen
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics / Q000378:metabolism*; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000187:drug effects / Q000378:metabolism; D004054:Diethylstilbestrol / Q000633:toxicity; D015536:Down-Regulation / Q000187:drug effects; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D006801:Humans; D010636:Phenols / Q000633:toxicity*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D001559:Benzhydryl Compounds; D004054:Diethylstilbestrol; D004967:Estrogens; D010636:Phenols; D012333:RNA, Messenger; D011960:Receptors, Estrogen; C041594:4-nonylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: BCRP; Diethylstilbestrol; Endocrine disruptors; Estrogen receptors; Human placenta; Xenobiotic transporters