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.

Effects of Cadmium, Lead, and Mercury on the Structure and Function of Reproductive Organs

“…These authors also confirmed that mercury (HgCl 2 ) produced a concentration-dependent uterotonic effect. This study shows that mercury evidently interacts with muscarinic receptors and activates calcium signaling cascades involving calcium channels, Rho-kinase, protein kinase-C, and phospholipase-C pathways to exert an uterotonic effect in rats [ 169 ].…”

“…In another human study, elevated mercury concentrations were observed in the hyperplasia tissue samples from pre-menopausal women, aged less than 50 years, who had different endometrial pathologies: typical endometrial hyperplasia, endometrial cancer and normal endometrial tissues [ 169 ].…”

Hepatoprotective Effect of Costus Afer on Trace Metal Mixture Treated Rats Mediated by Regulation of Oxidative Stress Markers, Inflammatory Cytokines and Bio-Metal Chelation

“…The signi cant increment (p < 0.05) seen in the rats received tracemetal mixture TMM with respect to ALT, AST, ALP, total and direct bilirubin levels which formed the markers of injury to the hepatocyte could be arise from increased membrane permeability and cell loss due to membrane oxidation (Iniaghe et al Many previous studies described trace metals as immune-suppressors that result in elevated levels of TNF-α, Il-1β and IL-6(pro-in ammatory cytokines). The elevated level of pro-in ammatory cytokine in this study may be due to heightened production of reactive oxygen species (Gao 2012;Guyot et al 2015). Oxidative stress could be associated with an excessive production of the pro-in ammatory cytokines (Gao 2012).…”

Whole Genome Pathway Analysis Identifies an Association of Cadmium Response Gene Loss with Copy Number Variation in Mutant p53 Bearing Uterine Endometrial Carcinomas

“…Cells in the uterus with a loss in the CR pathway would selectively uptake cadmium without any sequestration from molecular machinery, allowing this carcinogen to wreak further havoc and initiate oncogenesis. While this link of metallothionein proteins to cadmium appears important, it should be noted that metallothioneins sequester a number of heavy metal ions which may impact endometrial biology [ 40 , 41 ]. Metallothioneins also act to buffer zinc [ 42 ], impacting both enzymatic and transcriptional activities within the cell.…”