Melatonin: The watchdog of villous trophoblast homeostasis against hypoxia/reoxygenation-induced oxidative stress and apoptosis

Human placenta produces melatonin and expresses its receptors. We propose that melatonin, an antioxidant, protects the human placenta against hypoxia/reoxygenation (H/R)-induced damage. Primary term villous cytotrophoblasts were cultured under normoxia (8% O-2 with or without 1 mM melatonin for 72 h to induce differentiation into the syncytiotrophoblast. The cells were then cultured for an additional 22 h under normoxia or subjected to hypoxia (0.5% O-2) for 4 h followed by 18 h reoxygenation (8% O-2) with or without melatonin. H/R induced oxidative stress, which activated the Bax/Bcl-2 mitochondrial apoptosis pathway and the downstream fragmentation of DNA. Villous trophoblast treatment with melatonin reversed all the negative effects induced by H/R to normoxic levels. This study shows that melatonin protects the villous trophoblast against H/R-induced oxidative stress and apoptosis and suggests a potential preventive and therapeutic use of this indolamine in pregnancy complications characterized by syncytiotrophoblast survival alteration. (C) 2013 Elsevier Ireland Ltd. All rights reserved.