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

E Sieppi; K Vähäkangas; A Rautio; F Ietta; L Paulesu; P Myllynen

doi:10.1016/j.mce.2016.03.034

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

Mol Cell Endocrinol. 2016 Jul 5:429:41-9. doi: 10.1016/j.mce.2016.03.034. Epub 2016 Mar 30.

Authors

E Sieppi¹, K Vähäkangas², A Rautio³, F Ietta⁴, L Paulesu⁵, P Myllynen⁶

Affiliations

¹ 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.
² 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.
³ 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.
⁴ Department of Life Sciences, University of Siena, Via Aldo Moro 2, 53100, Siena, Italy. Electronic address: ietta@unisi.it.
⁵ Department of Life Sciences, University of Siena, Via Aldo Moro 2, 53100, Siena, Italy. Electronic address: luana.riccipaulesu@unisi.it.
⁶ 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.

PMID: 27036933
DOI: 10.1016/j.mce.2016.03.034

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.

Keywords: BCRP; Diethylstilbestrol; Endocrine disruptors; Estrogen receptors; Human placenta; Xenobiotic transporters.

MeSH terms

ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics
ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism*
Benzhydryl Compounds / toxicity*
Cells, Cultured
Chorionic Villi / drug effects
Chorionic Villi / metabolism
Diethylstilbestrol / toxicity
Down-Regulation / drug effects
Estrogens / toxicity*
Female
Humans
Phenols / toxicity*
Placenta / drug effects
Placenta / metabolism*
Pregnancy
Pregnancy Trimester, First / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptors, Estrogen / antagonists & inhibitors
Receptors, Estrogen / metabolism

Substances

ATP Binding Cassette Transporter, Subfamily G, Member 2
Benzhydryl Compounds
Estrogens
Phenols
RNA, Messenger
Receptors, Estrogen
Diethylstilbestrol
4-nonylphenol
bisphenol A