PMID- 25673501 OWN - NLM STAT- MEDLINE DCOM- 20160516 LR - 20181113 IS - 1096-0929 (Electronic) IS - 1096-6080 (Print) IS - 1096-0929 (Linking) VI - 145 IP - 1 DP - 2015 May TI - Supplementation with vitamin D3 during pregnancy protects against lipopolysaccharide-induced neural tube defects through improving placental folate transportation. PG - 90-7 LID - 10.1093/toxsci/kfv036 [doi] AB - Several reports demonstrated that maternal lipopolysaccharide (LPS) exposure at middle gestational stage caused neural tube defects (NTDs). This study investigated the effects of supplementation with vitamin D3 (VitD3) during pregnancy on LPS-induced NTDs. Pregnant mice except controls were ip injected with LPS (25 mug/kg) daily from gestational day (GD)8 to GD12. In LPS+VitD3 group, pregnant mice were orally administered with VitD3 (25 mug/kg) before LPS injection. As expected, a 5-day LPS injection resulted in 62.5% (10/16) of dams and 20.3% of fetuses with NTDs. Additional experiment showed that a 5-day LPS injection downregulated placental proton-coupled folate transporter (pcft) and reduced folate carrier 1 (rfc1), 2 major folate transporters in placentas. Consistent with downregulation of placental folate transporters, folate transport from maternal circulation into embryos was disturbed in LPS-treated mice. Interestingly, VitD3 not only inhibited placental inflammation but also attenuated LPS-induced downregulation of placental folate transporters. Correspondingly, VitD3 markedly improved folate transport from maternal circulation into the embryos. Importantly, supplementation with VitD3 during pregnancy protected mice from LPS-induced NTDs. Taken together, these results suggest that supplementation with VitD3 during pregnancy prevents LPS-induced NTDs through inhibiting placental inflammation and improving folate transport from maternal circulation into the embryos. CI - (c) The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. FAU - Chen, Yuan-Hua AU - Chen YH AD - *Department of Toxicology, Anhui Provincial Key Laboratory of Population Health & Aristogenics, School of Basic Medical Science and School of Life Science, Anhui Medical University, Hefei 230032, China *Department of Toxicology, Anhui Provincial Key Laboratory of Population Health & Aristogenics, School of Basic Medical Science and School of Life Science, Anhui Medical University, Hefei 230032, China *Department of Toxicology, Anhui Provincial Key Laboratory of Population Health & Aristogenics, School of Basic Medical Science and School of Life Science, Anhui Medical University, Hefei 230032, China. FAU - Yu, Zhen AU - Yu Z AD - *Department of Toxicology, Anhui Provincial Key Laboratory of Population Health & Aristogenics, School of Basic Medical Science and School of Life Science, Anhui Medical University, Hefei 230032, China *Department of Toxicology, Anhui Provincial Key Laboratory of Population Health & Aristogenics, School of Basic Medical Science and School of Life Science, Anhui Medical University, Hefei 230032, China. FAU - Fu, Lin AU - Fu L AD - *Department of Toxicology, Anhui Provincial Key Laboratory of Population Health & Aristogenics, School of Basic Medical Science and School of Life Science, Anhui Medical University, Hefei 230032, China. FAU - Xia, Mi-Zhen AU - Xia MZ AD - *Department of Toxicology, Anhui Provincial Key Laboratory of Population Health & Aristogenics, School of Basic Medical Science and School of Life Science, Anhui Medical University, Hefei 230032, China. FAU - Zhao, Mei AU - Zhao M AD - *Department of Toxicology, Anhui Provincial Key Laboratory of Population Health & Aristogenics, School of Basic Medical Science and School of Life Science, Anhui Medical University, Hefei 230032, China. FAU - Wang, Hua AU - Wang H AD - *Department of Toxicology, Anhui Provincial Key Laboratory of Population Health & Aristogenics, School of Basic Medical Science and School of Life Science, Anhui Medical University, Hefei 230032, China *Department of Toxicology, Anhui Provincial Key Laboratory of Population Health & Aristogenics, School of Basic Medical Science and School of Life Science, Anhui Medical University, Hefei 230032, China. FAU - Zhang, Cheng AU - Zhang C AD - *Department of Toxicology, Anhui Provincial Key Laboratory of Population Health & Aristogenics, School of Basic Medical Science and School of Life Science, Anhui Medical University, Hefei 230032, China. FAU - Hu, Yong-Fang AU - Hu YF AD - *Department of Toxicology, Anhui Provincial Key Laboratory of Population Health & Aristogenics, School of Basic Medical Science and School of Life Science, Anhui Medical University, Hefei 230032, China. FAU - Tao, Fang-Biao AU - Tao FB AD - *Department of Toxicology, Anhui Provincial Key Laboratory of Population Health & Aristogenics, School of Basic Medical Science and School of Life Science, Anhui Medical University, Hefei 230032, China xudex@126.com. FAU - Xu, De-Xiang AU - Xu DX AD - *Department of Toxicology, Anhui Provincial Key Laboratory of Population Health & Aristogenics, School of Basic Medical Science and School of Life Science, Anhui Medical University, Hefei 230032, China *Department of Toxicology, Anhui Provincial Key Laboratory of Population Health & Aristogenics, School of Basic Medical Science and School of Life Science, Anhui Medical University, Hefei 230032, China xudex@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150210 PL - United States TA - Toxicol Sci JT - Toxicological sciences : an official journal of the Society of Toxicology JID - 9805461 RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 1C6V77QF41 (Cholecalciferol) RN - 935E97BOY8 (Folic Acid) SB - IM MH - Animals MH - Chemokines/metabolism MH - Cholecalciferol/*administration & dosage MH - Cytokines/metabolism MH - *Dietary Supplements MH - Female MH - Folic Acid/*metabolism MH - Lipopolysaccharides/*toxicity MH - Maternal-Fetal Exchange MH - Mice MH - Mice, Inbred ICR MH - Neural Tube Defects/*prevention & control MH - Placenta/*metabolism MH - Pregnancy MH - Up-Regulation PMC - PMC4833037 OTO - NOTNLM OT - folic acid OT - lipopolysaccharide OT - neural tube defects OT - proton-coupled folate transporter OT - reduced folate carrier OT - vitamin D3 EDAT- 2015/02/13 06:00 MHDA- 2016/05/18 06:00 PMCR- 2016/05/01 CRDT- 2015/02/13 06:00 PHST- 2015/02/13 06:00 [entrez] PHST- 2015/02/13 06:00 [pubmed] PHST- 2016/05/18 06:00 [medline] PHST- 2016/05/01 00:00 [pmc-release] AID - kfv036 [pii] AID - 10.1093/toxsci/kfv036 [doi] PST - ppublish SO - Toxicol Sci. 2015 May;145(1):90-7. doi: 10.1093/toxsci/kfv036. Epub 2015 Feb 10.