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.


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


  • 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.