title: Low concentrations of Bisphenol A and para-Nonylphenol affect extravillous pathway of human trophoblast cells.
abstract: Bisphenol A (BPA) and para-Nonylphenol (p-NP) are chemicals of industrial origin which may influence human reproductive health. The effects of these substances in the prenatal life is an important topic that is receiving greater attention in the developed countries. In this study, human trophoblast cells HTR-8/SVneo were exposed to BPA and p-NP (1 × 10(-15), 1 × 10(-13), 1 × 10(-11), 1 × 10(-9) and 1 × 10(-7) M) and incubated for 24, 48 and/or 72 h then, examined for the main physiological processes which characterize the extravillous trophoblast. Cell proliferation showed no changes while the processes of cell migration and invasion were both reduced by BPA and p-NP. For each chemical, the activity was higher at lower concentrations with a maximum activity between 1 × 10(-13) and 1 × 10(-11) M (p < 0.05 for 1 × 10(-9) and p < 0.001 for 1 × 10(-11) M). Co-culture studies with human umbilical cord endothelial cells (HUVEC) revealed that trophoblast/endothelial interaction was significantly reduced by p-NP at 1 × 10(-11) M. Moreover, both chemicals were inducing differentiation of HTR-8/SVneo toward polyploidy by the process of endoreduplication. The estrogen-receptor antagonist ICI significantly reduced p-NP action, while it had no effect on BPA treated cells. In conclusion, p-NP and BPA act on trophoblast cells altering key physiological processes in placenta development. The exact mechanism of action of the chemicals in human trophoblast still needs to be clarified.
authors.affiliation: Department of Life Sciences, University of Siena, Via A. Moro 4, 53100 Siena, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Spagnoletti
authors.affiliation: Department of Life Sciences, University of Siena, Via A. Moro 4, 53100 Siena, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Paulesu
authors.affiliation: Department of Life Sciences, University of Siena, Via A. Moro 4, 53100 Siena, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Mannelli
authors.affiliation: Department of Life Sciences, University of Siena, Via A. Moro 4, 53100 Siena, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Ermini
authors.affiliation: Department of Life Sciences, University of Siena, Via A. Moro 4, 53100 Siena, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Romagnoli
authors.affiliation: Department of Medicine, Surgery and Neuroscience, Policlinico Santa Maria alle Scotte, Viale Mario Bracci, 53100 Siena, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Cintorino
authors.affiliation: Department of Life Sciences, University of Siena, Via A. Moro 4, 53100 Siena, Italy. Electronic address: ietta@unisi.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ietta
mesh_terms: D001559:Benzhydryl Compounds / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D018920:Coculture Techniques; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000378:metabolism; D052244:Endocrine Disruptors / Q000633:toxicity*; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology; D006801:Humans; D010636:Phenols / Q000633:toxicity*; D014327:Trophoblasts / Q000187:drug effects / Q000502:physiology*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D050761:Cyclin-Dependent Kinase Inhibitor p57; D052244:Endocrine Disruptors; D010636:Phenols; C493964:CDKN1C protein, human; C041594:4-nonylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Endocrine disruptors; Human placenta; Placenta development; Reproductive health; Trophoblast differentiation