Troglitazone attenuates hypoxia-induced injury in cultured term human trophoblasts.

Abstract

The purpose of this study was to test the hypothesis that the thiazolidinedione troglitazone, a peroxisome proliferator activated receptor-gamma ligand, attenuates hypoxia-induced trophoblast injury. Cytotrophoblasts from 4 term human placentas were cultured in the presence or absence of 10 mumol/L troglitazone in either 20% oxygen (standard conditions) or 1% oxygen (hypoxic conditions) for variable periods before cell harvest. Medium beta-human chorionic gonadotropin and human placental lactogen were analyzed by enzyme-linked immunosorbent assay. Apoptosis was quantified by cytokeratin-18 cleavage products staining; p53 expression was examined by Western blot analysis. beta-human chorionic gonadotropin and human placental lactogen levels were >/=2-fold higher in troglitazone-exposed cells at 16 hours of hypoxia, compared with vehicle control cells ( P <.05). The apoptotic index was reduced by >/=30% ( P <.001), and the expression of p53 was 2-fold lower ( P <.02) in troglitazone-exposed cells under hypoxia for </=16 hours but not different after >24 hours of low oxygen. Troglitazone attenuates the influence of acute hypoxia on cultured term human trophoblasts.