Fu Lin, Yu Zhen, Chen Yuan-Hua, Xia Mi-Zhen, Wang Hua, Zhang Cheng, Tao Fang-Biao, Xu De-Xiang
Department of Toxicology, Anhui Medical University, Hefei, China; Anhui Provincial Key Laboratory of Population Health & Aristogenics, Anhui Medical University, Hefei, China.
Department of Toxicology, Anhui Medical University, Hefei, China.
PLoS One. 2014 Nov 24;9(11):e113763. doi: 10.1371/journal.pone.0113763. eCollection 2014.
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.
脂多糖（LPS）与不良妊娠结局有关，包括啮齿动物的胎儿死亡、宫内生长受限（IUGR）、神经管缺陷（NTDs）和早产。先前的研究表明，褪黑素可预防LPS诱导的胎儿死亡、IUGR和早产。本研究的目的是探讨褪黑素对LPS诱导的NTDs的影响。除对照组外，所有怀孕小鼠从妊娠第8天（GD8）至第12天（GD12）每天腹腔注射LPS（25μg/kg）。一些怀孕小鼠在每次注射LPS前口服褪黑素（MT，50mg/kg）。连续五天注射LPS导致27.5%的胎儿出现无脑儿、脑膨出或脑膜膨出。额外的实验表明，母体暴露于LPS会显著下调胎盘质子偶联叶酸转运体（pcft），并扰乱叶酸从母体循环通过胎盘进入胎儿的转运。有趣的是，褪黑素显著减轻了LPS诱导的胎盘pcft下调。此外，褪黑素显著改善了叶酸从母体循环通过胎盘进入胎儿的转运。相应地，口服褪黑素降低了LPS诱导的无脑儿、脑膨出或脑膜膨出的发生率。综上所述，这些结果表明，口服褪黑素可通过减轻LPS诱导的叶酸从母体循环通过胎盘进入胎儿的转运障碍来预防LPS诱导的NTDs。
