Several epidemiological studies suggest an association between vitamin D deficiency (VDD) and fetal intrauterine growth restriction (IUGR). Here, we explored the mechanism through which VDD induced fetal IUGR. Pregnant mice were fed with VDD diet to establish VDD model. Cyp27b1^+/− mice were generated to develop a model of active vitamin D3 deficiency. Cyp27b1^+/− mice were injected with either 1α,25(OH)₂D₃ or vehicle once a day throughout pregnancy. As expected, fetal weight and crown-rump length were reduced in VDD diet-fed mice. Correspondingly, fetal weight and crown-rump length were lower in cyp27b1^+/− mice. 1α,25(OH)₂D₃ elevated fetal weight and crown-rump length, and protected cyp27b1^+/− mice from fetal IUGR. Further analysis found that placental proliferation was inhibited and placental weight was decreased in VDD diet-fed mice. Several growth factors and nutrient transfer pumps were downregulated in the placentas of VDD diet-fed mice. Mechanistically, several inflammatory cytokines were upregulated and placental NF-κB was activated not only in VDD diet-fed mice but also in VDD pregnant women. Interestingly, 1α,25(OH)₂D₃ inhibited the downregulated of placental nutrient transfer pumps and the upregulated of placental inflammatory cytokines in Cyp27b1+/- mice. These results provide experimental evidence that gestational VDD causes placental insufficiency and fetal IUGR may be through inducing placental inflammation.

几项流行病学研究表明，维生素D缺乏症（VDD）与胎儿宫内生长受限（IUGR）之间存在关联。在这里，我们探讨了VDD诱导胎儿IUGR的机制。给怀孕的小鼠喂食VDD饮食以建立VDD模型。生成Cyp27b1 ^+/-小鼠以建立活性维生素D3缺乏症模型。在整个怀孕期间，每天向Cyp27b1 ^+/-小鼠注射1α，25（OH）₂ D ₃或赋形剂。正如预期的那样，在VDD饮食喂养的小鼠中，胎儿的体重和冠臀的长度减少了。相应地，cyp27b1 ^+/-小鼠的胎儿体重和冠臀长度较低。1α，25（羟基）₂ D ₃胎儿体重和冠臀长升高，并保护cyp27b1 ^+/-小鼠免受胎儿IUGR侵害。进一步的分析发现，在VDD饮食喂养的小鼠中胎盘增殖受到抑制，胎盘重量减少。VDD饮食喂养的小鼠的胎盘中一些生长因子和营养转移泵被下调。从机理上讲，不仅在VDD饮食喂养的小鼠中，而且在VDD孕妇中，几种炎性细胞因子也被上调，胎盘NF-κB被激活。有趣的是，Cyp27b1 +/-中的1α，25（OH）₂ D ₃抑制了胎盘营养素输送泵的下调和胎盘炎性细胞因子的上调。老鼠。这些结果提供了实验证据，表明妊娠VDD会引起胎盘功能不全，而胎儿IUGR可能是通过诱发胎盘炎症而引起的。