title: Supplementation with vitamin D3 during pregnancy protects against lipopolysaccharide-induced neural tube defects through improving placental folate transportation.
abstract: 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 μg/kg) daily from gestational day (GD)8 to GD12. In LPS+VitD3 group, pregnant mice were orally administered with VitD3 (25 μg/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.
authors: *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.
authors: Yuan-Hua
authors: YH
authors: Chen
authors: *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.
authors: Zhen
authors: Z
authors: Yu
authors: *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.
authors: Lin
authors: L
authors: Fu
authors: *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.
authors: Mi-Zhen
authors: MZ
authors: Xia
authors: *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.
authors: Mei
authors: M
authors: Zhao
authors: *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.
authors: Hua
authors: H
authors: Wang
authors: *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.
authors: Cheng
authors: C
authors: Zhang
authors: *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.
authors: Yong-Fang
authors: YF
authors: Hu
authors: *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.
authors: Fang-Biao
authors: FB
authors: Tao
authors: *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.
authors: De-Xiang
authors: DX
authors: Xu
mesh_terms: D000818:Animals; D018925:Chemokines / Q000378:metabolism; D002762:Cholecalciferol / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008431:Maternal-Fetal Exchange; D051379:Mice; D008813:Mice, Inbred ICR; D009436:Neural Tube Defects / Q000517:prevention & control*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D015854:Up-Regulation
chemical_list: D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D002762:Cholecalciferol; D005492:Folic Acid
keywords: folic acid; lipopolysaccharide; neural tube defects; proton-coupled folate transporter; reduced folate carrier; vitamin D3