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

Abstract

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% O2) with or without 1mM melatonin for 72h to induce differentiation into the syncytiotrophoblast. The cells were then cultured for an additional 22h under normoxia or subjected to hypoxia (0.5% O2) for 4h followed by 18h reoxygenation (8% O2) 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.

Potential Utility of Melatonin in Preeclampsia, Intrauterine Fetal Growth Retardation, and Perinatal Asphyxia

“…Furthermore, this hormone reduces the loss of villous cytotrophoblasts by preventing apoptosis of these cells. 21 These data, together with the finding that transcripts of the melatoninsynthesizing enzymes and MT1 and MT2 melatonin receptors are present in human placenta, 22 suggest that melatonin may behave as a local regulator of placental function in an autocrine/paracrine manner.…”

Melatonin Reduces Projection Neuronal Injury Induced by 3-Nitropropionic Acid in the Rat Striatum

“…The antioxidant action of MT holds much interest in terms of its neuroprotective role in neurodegenerative disorders [12]. Moreover, MT has been proved to be useful in overwhelming neurotoxicity caused by quinolinic acid, to reduce lipid peroxidation and oxidative damage to nuclear DNA both in vivo and in vitro [13], to reduce neural damage in Alzheimer's disease (AD), to reduce oxidative damage in several models of Parkinson's disease (PD), to protect against glutamate excitotoxicity, to reduce ischemia-reperfusion injury and to lower neural damage caused by d-aminolevulinic acid and a variety of other neural toxins [14,15,16]. …”

The role of melatonin in development of gestational diabetes mellitus

“…Прежде всего, мелатонин и его метаболиты функционируют как прямые поглотители образующихся при беременности свободных радикалов, стимули-руют антиоксидантные ферменты, обеспечивая тем самым устойчивую защиту от свободнора-дикального повреждения на клеточном и тка-невом уровнях в единой системе мать -плацен-та -плод [64][65][66].…”