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

Erwan Guyot; Yevgeniya Solovyova; Céline Tomkiewicz; Alix Leblanc; Stéphane Pierre; Souleiman El Balkhi; Marie-Aude Le Frère-Belda; Fabrice Lecuru; Joël Poupon; Robert Barouki; Martine Aggerbeck; Xavier Coumoul

doi:10.1371/journal.pone.0142590

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

PLoS One. 2015 Nov 23;10(11):e0142590. doi: 10.1371/journal.pone.0142590. eCollection 2015.

Authors

Erwan Guyot^{1

2}, Yevgeniya Solovyova^{1

2

3}, Céline Tomkiewicz^{1

2}, Alix Leblanc^{1

2}, Stéphane Pierre^{1

2}, Souleiman El Balkhi⁴, Marie-Aude Le Frère-Belda^{1

5

2}, Fabrice Lecuru^{1

5

2}, Joël Poupon⁴, Robert Barouki^{1

2

6}, Martine Aggerbeck^{1

2}, Xavier Coumoul^{1

2}

Affiliations

¹ INSERM UMR-S 1124, Toxicologie Pharmacologie et Signalisation Cellulaire, 45 rue des Saints Pères, 75006 Paris, France.
² Université Paris Descartes, Paris Sorbonne Cité, Centre universitaire des Saints-Pères, 45 rue des Saints Pères, 75006 Paris, France.
³ 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.
⁴ Laboratoire de toxicologie biologique, AP-HP, Hôpital Lariboisière, 2, rue Ambroise Paré, 75475 Paris, France.
⁵ Service de chirurgie gynécologique et cancérologique, hôpital européen Georges-Pompidou, AP-HP, 20, rue Leblanc, 75015 Paris, France.
⁶ AP-HP, Hôpital Necker-Enfants Malades, service de biochimie métabolique, 149, rue de Sèvres, 75743 Paris, France.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Basic Helix-Loop-Helix Transcription Factors / metabolism
Biopsy
Cadherins / metabolism
Cell Differentiation
Cell Line, Tumor
Cell Survival
Cytochrome P-450 CYP1A1 / metabolism
Cytochrome P-450 CYP1B1 / biosynthesis
Endometrium / chemistry
Endometrium / pathology*
Female
Gene Expression Regulation, Neoplastic*
Heme Oxygenase-1 / metabolism
Humans
Mercury / analysis*
Metals, Heavy / analysis*
NAD(P)H Dehydrogenase (Quinone) / metabolism
Oxidative Stress
Phenotype
Polychlorinated Dibenzodioxins / analogs & derivatives*
Polychlorinated Dibenzodioxins / chemistry
RNA, Messenger / metabolism
Reactive Oxygen Species / metabolism
Receptors, Aryl Hydrocarbon / metabolism
Snail Family Transcription Factors
Transcription Factors / metabolism
Vimentin / metabolism

Substances

AHR protein, human
Basic Helix-Loop-Helix Transcription Factors
Cadherins
Metals, Heavy
Polychlorinated Dibenzodioxins
RNA, Messenger
Reactive Oxygen Species
Receptors, Aryl Hydrocarbon
Snail Family Transcription Factors
Transcription Factors
Vimentin
1,2,7,8-tetrachlorodibenzo-p-dioxin
CYP1A1 protein, human
CYP1B1 protein, human
Cytochrome P-450 CYP1A1
Cytochrome P-450 CYP1B1
HMOX1 protein, human
Heme Oxygenase-1
NAD(P)H Dehydrogenase (Quinone)
NQO1 protein, human
Mercury

Grants and funding

This work was supported by ARC (Association pour la Recherche sur le Cancer, SFI20101201842); the CNRS (Centre National de la recherche scientifique, Martine Aggerbeck); INCa (Institut National du Cancer); INSERM (Institut National de la Santé et de la Recherche Médicale, Céline Tomkiewicz); the Ministère de l’enseignement supérieur et de la recherche (Doctoral fellowship, Alix Leblanc); the Région Ile de France (Doctoral fellowship, Dr Stéphane Pierre); the Université Paris Descartes and PRES (Pr Xavier Coumoul); the Assistance Publique (AP/HP; Dr Erwan Guyot); the Institute of Urgent and Recovery Surgery (Dr Y. Solovyova). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.