Orally administered melatonin prevents lipopolysaccharide-induced neural tube defects in mice.
Orally administered melatonin prevents lipopolysaccharide-induced neural tube defects in mice.
复制标题
DOI：
10.1371/journal.pone.0113763
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Xu DX
中科院分区：
文献类型：
--
作者：
Fu L;Yu Z;Chen YH;Xia MZ;Wang H;Zhang C;Tao FB;Xu DX
脂多糖(LPS)与不良妊娠结局有关，包括胎儿死亡、宫内生长受限(IUGR)、神经管畸形(NTDS)和啮齿动物早产。先前的研究表明，褪黑素对脂多糖诱导的胎儿死亡、宫内发育迟缓和早产具有保护作用。本研究的目的是探讨褪黑素对内毒素诱导的NTDS的影响。除对照组外，所有妊娠小鼠均于妊娠第8天至第12天每天腹腔注射脂多糖(25µg/kg)。部分妊娠小鼠在每次注射脂多糖前灌胃褪黑激素(MT，50 mg/kg)。注射内毒素5天后，27.5%的胎儿出现无脑儿、脑外儿或脑膜脑膨出。另外的实验表明，母体内毒素暴露显著下调胎盘质子偶联叶酸转运体(PCFT)，并干扰叶酸从母体循环通过胎盘进入胎儿的运输。有趣的是，褪黑素显著减弱了内毒素诱导的胎盘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运输。相应地，口服褪黑素可降低脂多糖诱导的无脑、脑外畸形或脑膜脊膜膨出的发生率。综上所述，这些结果表明，口服褪黑素可以通过减轻脂多糖诱导的叶酸从母体循环通过胎盘进入胎儿的运输障碍来预防内毒素诱导的NTDS。
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.
登录
查看更多内容
影响因子：
3.8
作者：
Cherukad, J.;Wainwright, V.;Watson, E. D.
通讯作者：
Watson, E. D.
影响因子：
10.3
作者：
Schaefer, Meike;Hardeland, Rudiger
通讯作者：
Hardeland, Rudiger
影响因子：
9.8
作者：
Buhimschi, IA;Buhimschi, CS;Weiner, CP
通讯作者：
Weiner, CP
影响因子：
3.7
作者：
Farkas SA;Böttiger AK;Isaksson HS;Finnell RH;Ren A;Nilsson TK
通讯作者：
Nilsson TK
影响因子：
56.9
作者：
Fleming, A;Copp, AJ
通讯作者：
Copp, AJ