FERRITIN IN CULTURED HUMAN CYTOTROPHOBLASTS - SYNTHESIS AND SUBUNIT DISTRIBUTION

The present study aims at the role of ferritin in the regulation of sy ncytiotrophoblast free iron levels. The differentiated cytotrophoblast cell in culture is used as a model for this maternal-fetal interface. Cytotrophoblast cells isolated from term placentae are cultured in ir on-poor (Medium 199), iron-depleted ([desferrioxamine(DFO)] and iron-s upplemented [diferric transferrin (hTf-2Fe), ferric ammonium citrate ( FAC)] medium. Distribution and de novo synthesis of isoferritins is st udied together with the cellular iron concentration and the ferritin i ron saturation. Compared to ferritin isolated from total placenta, fer ritin obtained from villous tissue is enriched with acidic isoforms. T his observation is in agreement with measured! light (L) to heavy (H) subunit ratios <1 of de novo synthesized ferritin in cultured cytotrop hoblast cells. Neither iron-poor culture medium, nor hTf-2Fe supplemen ted medium affects the cellular iron ol ferritin concentration. FAC in creased the cellular ferritin iron saturation and (by synthesis) the a cidic isoferritin concentrations. The results strongly suggest, that t he term syncytiotrophoblast is able to balance transferrin-mediated ir on uptake and iron release. In case of FAC supplementation, the syncyt iotrophoblast is unable to Keep intracellular iron low, and ferritin s ynthesis is stimulated. The predominance of acidic ferritins and the p referential synthesis of H subunits can be functionally explained by t he established fact that iron incorporation in acidic ferritins is fas ter due to the presence of ferroxidase centres. Damage by free iron ca talysed hydroxyl radical formation is therefore minimized.