title: Folic acid protects against lipopolysaccharide-induced preterm delivery and intrauterine growth restriction through its anti-inflammatory effect in mice.
abstract: Increasing evidence demonstrates that maternal folic acid (FA) supplementation during pregnancy reduces the risk of neural tube defects, but whether FA prevents preterm delivery and intrauterine growth restriction (IUGR) remains obscure. Previous studies showed that maternal lipopolysaccharide (LPS) exposure induces preterm delivery, fetal death and IUGR in rodent animals. The aim of this study was to investigate the effects of FA on LPS-induced preterm delivery, fetal death and IUGR in mice. Some pregnant mice were orally administered with FA (0.6, 3 or 15 mg/kg) 1 h before LPS injection. As expected, a high dose of LPS (300 μg/kg, i.p.) on gestational day 15 (GD15) caused 100% of dams to deliver before GD18 and 89.3% of fetuses dead. A low dose of LPS (75 μg/kg, i.p.) daily from GD15 to GD17 resulted in IUGR. Interestingly, pretreatment with FA prevented LPS-induced preterm delivery and fetal death. In addition, FA significantly attenuated LPS-induced IUGR. Further experiments showed that FA inhibited LPS-induced activation of nuclear factor kappa B (NF-κB) in mouse placentas. Moreover, FA suppressed LPS-induced NF-κB activation in human trophoblast cell line JEG-3. Correspondingly, FA significantly attenuated LPS-induced upregulation of cyclooxygenase (COX)-2 in mouse placentas. In addition, FA significantly reduced the levels of interleukin (IL)-6 and keratinocyte-derived cytokine (KC) in amniotic fluid of LPS-treated mice. Collectively, maternal FA supplementation during pregnancy protects against LPS-induced preterm delivery, fetal death and IUGR through its anti-inflammatory effects.
authors: Department of Toxicology, Anhui Medical University, Hefei, Anhui, China ; Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei, Anhui, China ; School of Nursing, Anhui Medical University, Hefei, Anhui, China.
authors: Mei
authors: M
authors: Zhao
authors: Yuan-Hua
authors: YH
authors: Chen
authors: Xu-Ting
authors: XT
authors: Dong
authors: Jun
authors: J
authors: Zhou
authors: Xue
authors: X
authors: Chen
authors: Hua
authors: H
authors: Wang
authors: Shu-Xian
authors: SX
authors: Wu
authors: Mi-Zhen
authors: MZ
authors: Xia
authors: Cheng
authors: C
authors: Zhang
authors: De-Xiang
authors: DX
authors: Xu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005313:Fetal Death / Q000139:chemically induced / Q000517:prevention & control; D005317:Fetal Growth Retardation / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D005492:Folic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D047928:Premature Birth / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D020011:Protective Agents; D009569:Nitric Oxide; D005492:Folic Acid; D051546:Cyclooxygenase 2