title: Orally administered melatonin prevents lipopolysaccharide-induced neural tube defects in mice.
abstract: Lipopolysaccharide (LPS) has been associated with adverse pregnant outcomes, including fetal demise, intra-uterine growth restriction (IUGR), neural tube defects (NTDs) and preterm delivery in rodent animals. Previous studies demonstrated that melatonin protected against LPS-induced fetal demise, IUGR and preterm delivery. The aim of the present study was to investigate the effects of melatonin on LPS-induced NTDs. All pregnant mice except controls were intraperitoneally injected with LPS (25 µg/kg) daily from gestational day (GD)8 to GD12. Some pregnant mice were orally administered with melatonin (MT, 50 mg/kg) before each LPS injection. A five-day LPS injection resulted in 27.5% of fetuses with anencephaly, exencephaly or encephalomeningocele. Additional experiment showed that maternal LPS exposure significantly down-regulated placental proton-coupled folate transporter (pcft) and disturbed folate transport from maternal circulation through the placentas into the fetus. Interestingly, melatonin significantly attenuated LPS-induced down-regulation of placental pcft. Moreover, melatonin markedly improved the transport of folate from maternal circulation through the placentas into the fetus. Correspondingly, orally administered melatonin reduced the incidence of LPS-induced anencephaly, exencephaly or encephalomeningocele. Taken together, these results suggest that orally administered melatonin prevents LPS-induced NTDs through alleviating LPS-induced disturbance of folate transport from maternal circulation through the placenta into the fetus.
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China; Anhui Provincial Key Laboratory of Population Health & Aristogenics, Anhui Medical University, Hefei, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China; Anhui Provincial Key Laboratory of Population Health & Aristogenics, Anhui Medical University, Hefei, China.
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Chen
authors.affiliation: School of Life Science, Anhui Medical University, Hefei, China.
authors.forename: Mi-Zhen
authors.initials: MZ
authors.lastname: Xia
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China; Anhui Provincial Key Laboratory of Population Health & Aristogenics, Anhui Medical University, Hefei, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Anhui Provincial Key Laboratory of Population Health & Aristogenics, Anhui Medical University, Hefei, China.
authors.forename: Fang-Biao
authors.initials: FB
authors.lastname: Tao
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China; Anhui Provincial Key Laboratory of Population Health & Aristogenics, Anhui Medical University, Hefei, China.
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
mesh_terms: D000284:Administration, Oral; D000757:Anencephaly / Q000139:chemically induced / Q000196:embryology / Q000517:prevention & control; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D008588:Meningocele / Q000139:chemically induced / Q000196:embryology / Q000517:prevention & control; D008813:Mice, Inbred ICR; D009436:Neural Tube Defects / Q000139:chemically induced / Q000196:embryology / Q000517:prevention & control*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D058979:Proton-Coupled Folate Transporter / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000975:Antioxidants; D018925:Chemokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D058979:Proton-Coupled Folate Transporter; C505058:SLC46A1 protein, human; D005492:Folic Acid; D008550:Melatonin