Regulation of metallothionein expression in human amnion epithelial and mesenchymal cells

In this study the potential for metallothionein expression in amnion epithelial and mesenchymal cells in response to cadmium was evaluated.

Levels of metallothionein messenger ribonucleic acid were evaluated in freshly separated amnion epithelial and mesenchymal cells and in amnion cells in culture.

The levels of metallothionein messenger ribonucleic acid in human amnion mesenchymal cells freshly isolated after delivery of term pregnancies were greater than those in epithelial cells of the same tissue. The levels in mesenchymal cells in monolayer culture at confluence also were greater than those in confluent epithelial cells propagated from the same tissue. In response to treatment with cadmium (100 nmol/L to 50 micromol/L), which is inhaled in cigarette smoke, the levels of metallothionein messenger ribonucleic acid in both cell types increased markedly in a dose-dependent manner, but the level was greater in epithelial cells at all concentrations of cadmium chloride tested. With cadmium chloride (10 micromol/L), the level of metallothionein messenger ribonucleic acid increased by as much as 1000-fold in epithelial cells and 10-fold in mesenchymal cells compared with untreated (control) cells. Dexamethasone and tetradecanoyl phorbol acetate also acted to increase the levels in amnion epithelial and mesenchymal cells but not nearly to the levels effected by cadmium.

These findings are indicative that metallothionein expression in amnion epithelial cells is exquisitely sensitive to cadmium in concentrations similar to those in amniotic fluid of pregnancies of women who smoke cigarettes. We hypothesize that increased levels of metallothionein in amniotic fluid and amnion epithelial cells will bind and thereby may limit the availability of copper to the Cu++-dependent enzyme lysyl oxidase in mesenchymal cells and thereby impair the cross-linking of interstitial collagens, which is effected by this enzyme.