Chen Yuan-Hua, Yu Zhen, Fu Lin, Xia Mi-Zhen, Zhao Mei, Wang Hua, Zhang Cheng, Hu Yong-Fang, Tao Fang-Biao, Xu De-Xiang
*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.
*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.
Toxicol Sci. 2015 May;145(1):90-7. doi: 10.1093/toxsci/kfv036. Epub 2015 Feb 10.
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.
多项报告表明，孕期中期母体暴露于脂多糖（LPS）会导致神经管缺陷（NTDs）。本研究调查了孕期补充维生素D3（VitD3）对LPS诱导的NTDs的影响。除对照组外，怀孕小鼠从妊娠第8天（GD8）至GD12每天腹腔注射LPS（25μg/kg）。在LPS+VitD3组中，怀孕小鼠在注射LPS前口服VitD3（25μg/kg）。正如预期的那样，5天的LPS注射导致62.5%（10/16）的母鼠和20.3%的胎儿出现NTDs。额外的实验表明，5天的LPS注射下调了胎盘质子偶联叶酸转运体（pcft）并降低了叶酸载体1（rfc1），这是胎盘中两种主要的叶酸转运体。与胎盘叶酸转运体的下调一致，LPS处理的小鼠中母体循环到胚胎中的叶酸转运受到干扰。有趣的是，VitD3不仅抑制了胎盘炎症，还减弱了LPS诱导的胎盘叶酸转运体的下调。相应地，VitD3显著改善了母体循环到胚胎中的叶酸转运。重要的是，孕期补充VitD3可保护小鼠免受LPS诱导的NTDs。综上所述，这些结果表明，孕期补充VitD3可通过抑制胎盘炎症和改善母体循环到胚胎中的叶酸转运来预防LPS诱导的NTDs。
