PMID- 25420102
OWN - NLM
STAT- MEDLINE
DCOM- 20160126
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 11
DP  - 2014
TI  - Orally administered melatonin prevents lipopolysaccharide-induced neural tube 
      defects in mice.
PG  - e113763
LID - 10.1371/journal.pone.0113763 [doi]
LID - e113763
AB  - 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 microg/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.
FAU - Fu, Lin
AU  - Fu L
AD  - Department of Toxicology, Anhui Medical University, Hefei, China; Anhui 
      Provincial Key Laboratory of Population Health & Aristogenics, Anhui Medical 
      University, Hefei, China.
FAU - Yu, Zhen
AU  - Yu Z
AD  - Department of Toxicology, Anhui Medical University, Hefei, China.
FAU - Chen, Yuan-Hua
AU  - Chen YH
AD  - Department of Toxicology, Anhui Medical University, Hefei, China; Anhui 
      Provincial Key Laboratory of Population Health & Aristogenics, Anhui Medical 
      University, Hefei, China.
FAU - Xia, Mi-Zhen
AU  - Xia MZ
AD  - School of Life Science, Anhui Medical University, Hefei, China.
FAU - Wang, Hua
AU  - Wang H
AD  - Department of Toxicology, Anhui Medical University, Hefei, China; Anhui 
      Provincial Key Laboratory of Population Health & Aristogenics, Anhui Medical 
      University, Hefei, China.
FAU - Zhang, Cheng
AU  - Zhang C
AD  - Department of Toxicology, Anhui Medical University, Hefei, China.
FAU - Tao, Fang-Biao
AU  - Tao FB
AD  - Anhui Provincial Key Laboratory of Population Health & Aristogenics, Anhui 
      Medical University, Hefei, China.
FAU - Xu, De-Xiang
AU  - Xu DX
AD  - Department of Toxicology, Anhui Medical University, Hefei, China; Anhui 
      Provincial Key Laboratory of Population Health & Aristogenics, Anhui Medical 
      University, Hefei, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141124
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antioxidants)
RN  - 0 (Chemokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Proton-Coupled Folate Transporter)
RN  - 0 (SLC46A1 protein, human)
RN  - 935E97BOY8 (Folic Acid)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Administration, Oral
MH  - Anencephaly/chemically induced/embryology/prevention & control
MH  - Animals
MH  - Antioxidants/administration & dosage/pharmacology
MH  - Chemokines/genetics/metabolism
MH  - Female
MH  - Folic Acid/blood/metabolism
MH  - Gene Expression Regulation, Developmental/*drug effects
MH  - Inflammation Mediators/metabolism
MH  - Lipopolysaccharides
MH  - Male
MH  - Maternal-Fetal Exchange/drug effects
MH  - Melatonin/administration & dosage/*pharmacology
MH  - Meningocele/chemically induced/embryology/prevention & control
MH  - Mice, Inbred ICR
MH  - Neural Tube Defects/chemically induced/embryology/*prevention & control
MH  - Placenta/*metabolism
MH  - Pregnancy
MH  - Proton-Coupled Folate Transporter/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC4242665
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/11/25 06:00
MHDA- 2016/01/27 06:00
PMCR- 2014/11/24
CRDT- 2014/11/25 06:00
PHST- 2014/08/25 00:00 [received]
PHST- 2014/10/29 00:00 [accepted]
PHST- 2014/11/25 06:00 [entrez]
PHST- 2014/11/25 06:00 [pubmed]
PHST- 2016/01/27 06:00 [medline]
PHST- 2014/11/24 00:00 [pmc-release]
AID - PONE-D-14-37394 [pii]
AID - 10.1371/journal.pone.0113763 [doi]
PST - epublish
SO  - PLoS One. 2014 Nov 24;9(11):e113763. doi: 10.1371/journal.pone.0113763. 
      eCollection 2014.