title: Determination of Heavy Metal Concentrations in Normal and Pathological Human Endometrial Biopsies and In Vitro Regulation of Gene Expression by Metals in the Ishikawa and Hec-1b Endometrial Cell Line.
abstract: It is well known that several metals, such as lead, mercury, cadmium, and vanadium, can mimic the effects of estrogens (metallo-estrogens). Nevertheless, there are only a few studies that have assessed the effects of toxic metals on the female genital tract and, in particular, endometrial tissue. In this context, we measured the concentrations of several trace elements in human endometrial tissue samples from individuals with hyperplasia or adenocarcinoma and in normal tissues. Hyperplasic endometrial tissue has a 4-fold higher concentration of mercury than normal tissue. Mercury can affect both the AhR and ROS signaling pathways. Thus, we investigated the possible toxic effects of mercury by in vitro studies. We found that mercury increases oxidative stress (increased HO1 and NQO1 mRNA levels) and alters the cytoskeleton in the human endometrial Ishikawa cell line and to a lesser extent, in the "less-differentiated" human endometrial Hec-1b cells. The results might help to explain a potential link between this metal and the occurrence of endometrial hyperplasia.
authors.affiliation: INSERM UMR-S 1124, Toxicologie Pharmacologie et Signalisation Cellulaire, 45 rue des Saints Pères, 75006 Paris, France.|Université Paris Descartes, Paris Sorbonne Cité, Centre universitaire des Saints-Pères, 45 rue des Saints Pères, 75006 Paris, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Guyot
authors.affiliation: INSERM UMR-S 1124, Toxicologie Pharmacologie et Signalisation Cellulaire, 45 rue des Saints Pères, 75006 Paris, France.|Université Paris Descartes, Paris Sorbonne Cité, Centre universitaire des Saints-Pères, 45 rue des Saints Pères, 75006 Paris, France.|Institute of Urgent and Recovery Surgery named after V.K. Gusak of the Ukrainian Academy of Medical Sciences, Donetsk; 47, avenue Leninsky, Donetsk- 83045, Ukraine.
authors.forename: Yevgeniya
authors.initials: Y
authors.lastname: Solovyova
authors.affiliation: INSERM UMR-S 1124, Toxicologie Pharmacologie et Signalisation Cellulaire, 45 rue des Saints Pères, 75006 Paris, France.|Université Paris Descartes, Paris Sorbonne Cité, Centre universitaire des Saints-Pères, 45 rue des Saints Pères, 75006 Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Tomkiewicz
authors.affiliation: INSERM UMR-S 1124, Toxicologie Pharmacologie et Signalisation Cellulaire, 45 rue des Saints Pères, 75006 Paris, France.|Université Paris Descartes, Paris Sorbonne Cité, Centre universitaire des Saints-Pères, 45 rue des Saints Pères, 75006 Paris, France.
authors.forename: Alix
authors.initials: A
authors.lastname: Leblanc
authors.affiliation: INSERM UMR-S 1124, Toxicologie Pharmacologie et Signalisation Cellulaire, 45 rue des Saints Pères, 75006 Paris, France.|Université Paris Descartes, Paris Sorbonne Cité, Centre universitaire des Saints-Pères, 45 rue des Saints Pères, 75006 Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pierre
authors.affiliation: Laboratoire de toxicologie biologique, AP-HP, Hôpital Lariboisière, 2, rue Ambroise Paré, 75475 Paris, France.
authors.forename: Souleiman
authors.initials: S
authors.lastname: El Balkhi
authors.affiliation: INSERM UMR-S 1124, Toxicologie Pharmacologie et Signalisation Cellulaire, 45 rue des Saints Pères, 75006 Paris, France.|Service de chirurgie gynécologique et cancérologique, hôpital européen Georges-Pompidou, AP-HP, 20, rue Leblanc, 75015 Paris, France.|Université Paris Descartes, Paris Sorbonne Cité, Centre universitaire des Saints-Pères, 45 rue des Saints Pères, 75006 Paris, France.
authors.forename: Marie-Aude
authors.initials: MA
authors.lastname: Le Frère-Belda
authors.affiliation: INSERM UMR-S 1124, Toxicologie Pharmacologie et Signalisation Cellulaire, 45 rue des Saints Pères, 75006 Paris, France.|Service de chirurgie gynécologique et cancérologique, hôpital européen Georges-Pompidou, AP-HP, 20, rue Leblanc, 75015 Paris, France.|Université Paris Descartes, Paris Sorbonne Cité, Centre universitaire des Saints-Pères, 45 rue des Saints Pères, 75006 Paris, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lecuru
authors.affiliation: Laboratoire de toxicologie biologique, AP-HP, Hôpital Lariboisière, 2, rue Ambroise Paré, 75475 Paris, France.
authors.forename: Joël
authors.initials: J
authors.lastname: Poupon
authors.affiliation: INSERM UMR-S 1124, Toxicologie Pharmacologie et Signalisation Cellulaire, 45 rue des Saints Pères, 75006 Paris, France.|Université Paris Descartes, Paris Sorbonne Cité, Centre universitaire des Saints-Pères, 45 rue des Saints Pères, 75006 Paris, France.|AP-HP, Hôpital Necker-Enfants Malades, service de biochimie métabolique, 149, rue de Sèvres, 75743 Paris, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Barouki
authors.affiliation: INSERM UMR-S 1124, Toxicologie Pharmacologie et Signalisation Cellulaire, 45 rue des Saints Pères, 75006 Paris, France.|Université Paris Descartes, Paris Sorbonne Cité, Centre universitaire des Saints-Pères, 45 rue des Saints Pères, 75006 Paris, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Aggerbeck
authors.affiliation: INSERM UMR-S 1124, Toxicologie Pharmacologie et Signalisation Cellulaire, 45 rue des Saints Pères, 75006 Paris, France.|Université Paris Descartes, Paris Sorbonne Cité, Centre universitaire des Saints-Pères, 45 rue des Saints Pères, 75006 Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Coumoul
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001706:Biopsy; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1 / Q000096:biosynthesis; D004717:Endometrium / Q000737:chemistry / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D008628:Mercury / Q000032:analysis*; D019216:Metals, Heavy / Q000032:analysis*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D018384:Oxidative Stress; D010641:Phenotype; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D051547:Heme Oxygenase-1; D008628:Mercury; D019216:Metals, Heavy; D016660:NAD(P)H Dehydrogenase (Quinone); D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D018336:Receptors, Aryl Hydrocarbon; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014746:Vimentin; C111235:AHR protein, human; C445379:1,2,7,8-tetrachlorodibenzo-p-dioxin; C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human; C496541:HMOX1 protein, human; C447479:NQO1 protein, human