Melatonin Alleviates Lipopolysaccharide-induced Placental Cellular Stress Response In Mice

Objective Melatonin protects mice from lipopolysaccharide (LPS)-induced fetal deathand intra-uterine growth retardation. Nevertheless, its molecular mechanism remainsobscure. In the present study, we investigated the effects of melatonin on LPS-inducedcellular stress in placenta.Methods Pregnant mice were given with melatonin [5.0mg/kg, intraperitoneal (i.p.)]30min before and150min after LPS (300μg/kg, i.p.) on gestational day15. Oxidativestress, endoplasmic reticulum (ER) stress, hypoxic stress, and heat stress in placentawere analyzed at4hr after LPS.Results As expected, maternal LPS administration resulted in placental glutathione(GSH) depletion and up-regulated the expression of placental antioxidative enzymes. Inaddition, LPS significantly increased the level of inducible nitric oxide synthase (iNOS)and enhanced the intensity of placental3-nitrotyrosine residues. An ER stress, asdetermined by a decreased GRP78expression, an obvious eIF2and JNKphosphorylation, and an increased CHOP expression, were observed in placenta ofpregnant mice injected with LPS. In addition, LPS significantly increased mRNA levelof placental HIF-1, VEGF, and ET-1, the markers of hypoxic stress. Heme oxygenase(HO)-1, a marker of heat stress, was also up-regulated in placenta of LPS-treatedpregnant mice. Interestingly, LPS-induced placental oxidative stress, hypoxic stress, andER stress were significantly alleviated when pregnant mice were given with melatonin,whereas melatonin had little effect on LPS-evoked placental HO-1expression.Conclusion LPS-induced placental oxidative stress, ER stress, hypoxic stress and heatstress. Maternally administered melatonin alleviates LPS-induced cellular stress in theplacenta.