title: New in vitro biomarkers to detect toxicity in human placental cells: The example of benzo[A]pyrene.
abstract: Our aim was to study the toxicity of benzo(a)pyrene (BaP), an environmental pollutant that can reach placenta, on two human placental models in order to propose biomarkers in risk assessment for pregnancy. Ex vivo human placental cells isolated from term placenta and JEG-3 cancer cell line were incubated with BaP at 0.1-10 μM for 48 h or 72 h. BaP induced neither loss of cell viability nor apoptosis in ex vivo placental cells. To go further, we performed experiments on JEG-3 cell line that provides near-unlimited cells. The results we obtained in JEG-3 cells confirmed that BaP, in our experimental conditions, is neither necrotic nor apoptotic for placental cells. BaP toxicity on placental cells resulted in cell cycle arrest (G2/M phase) associated with inhibition of cell proliferation. Besides, we observed that BaP remodeled the protein content of membrane microdomains via increased expression of ZO-1, caveolin-1 and P2X7 cell degenerescence receptor. In conclusion, we identified nuclear and membrane potential biomarkers of risks for placenta and then pregnancy. These potential biomarkers detected on placental cell lines could represent useful tools for toxicological studies.
authors.affiliation: UMR 8638 CNRS COMETE, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75006 Paris, France; Fondation PremUp, 4 avenue de l'Observatoire, 75014 Paris, France.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Wakx
authors.affiliation: UMR 8638 CNRS COMETE, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75006 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Regazzetti
authors.affiliation: UMR 8638 CNRS COMETE, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75006 Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Dargère
authors.affiliation: UMR 8638 CNRS COMETE, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75006 Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Auzeil
authors.affiliation: Fondation PremUp, 4 avenue de l'Observatoire, 75014 Paris, France; INSERM U1139, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75006 Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gil
authors.affiliation: Fondation PremUp, 4 avenue de l'Observatoire, 75014 Paris, France; INSERM U1139, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75006 Paris, France.
authors.forename: Danièle
authors.initials: D
authors.lastname: Evain-Brion
authors.affiliation: UMR 8638 CNRS COMETE, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75006 Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Laprévote
authors.affiliation: UMR 8638 CNRS COMETE, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75006 Paris, France. Electronic address: patrice.rat@parisdescartes.fr.
authors.forename: Patrice
authors.initials: P
authors.lastname: Rat
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001564:Benzo(a)pyrene / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D006801:Humans; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D051242:Caveolin 1; D004785:Environmental Pollutants; D058486:Receptors, Purinergic P2X7; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D001564:Benzo(a)pyrene; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1
keywords: Benzo(a)pyrene; DNA damage; In vitro; P2X7 receptor; Placental cells; Toxicity