Glucose uptake by the placenta and its transfer to the fetus is a finely regulated process required for placental and fetal development. Deficient placentation is associated with pregnancy complications such as fetal growth restriction (FGR). The vasoactive intestinal peptide (VIP) has embryotrophic effects in mice and regulates human cytotrophoblast metabolism and function. Here we compared glucose uptake and transplacental transport in vivo by VIP-deficient placentas from normal or VIP-deficient maternal background. The role of endogenous VIP in placental glucose and amino acid uptake was also investigated. Wild type C57BL/6 (WT) or VIP^+/− (VIP HT) females were mated with WT, VIP knock-out (VIP KO) or VIP HT males. Glucose uptake and transplacental transport were evaluated by the injection of the fluorescent d-glucose analogue 2-NBDG in pregnant mice at gestational day (gd) 17.5. Glucose and amino acid uptake in vitro by placental explants were measured with 2-NBDG or ¹⁴C-MeAIB respectively. In normal VIP maternal background, fetal weight was reduced in association with placental VIP deficiency, whereas placental weight was unaltered. Paradoxically, VIP^+/− placentas presented higher glucose uptake and higher gene expression of GLUT1 and mTOR than VIP^+/+ placentas. However, in a maternal VIP-deficient environment placental uptake and transplacental transport of glucose increased while fetal weights were unaffected, regardless of feto-placental genotype. Results point to VIP-deficient pregnancy in a normal background as a suitable FGR model with increased placental glucose uptake and transplacental transport. The apparently compensatory actions are unable to sustain normal fetal growth and could result in complications later in life.

胎盘摄取葡萄糖并将其转移到胎儿是胎盘和胎儿发育所需的精细调节过程。胎盘不足与妊娠并发症有关，例如胎儿生长受限 (FGR)。血管活性肠肽 (VIP) 在小鼠中具有胚胎营养作用，并调节人类细胞滋养层的代谢和功能。在这里，我们比较了来自正常或 VIP 缺陷母体背景的 VIP 缺陷胎盘在体内的葡萄糖摄取和经胎盘转运。还研究了内源性 VIP 在胎盘葡萄糖和氨基酸摄取中的作用。野生型 C57BL/6 (WT) 或 VIP ^+/-(VIP HT) 雌性与 WT、VIP 敲除 (VIP KO) 或 VIP HT 雄性交配。通过在妊娠日 (gd) 17.5 在怀孕小鼠中注射荧光d-葡萄糖类似物 2-NBDG来评估葡萄糖摄取和经胎盘转运。分别用 2-NBDG 或¹⁴ C-MeAIB测量体外胎盘外植体对葡萄糖和氨基酸的摄取。在正常的 VIP 母体背景下，胎儿体重降低与胎盘 VIP 缺乏相关，而胎盘重量未改变。矛盾的是，VIP ^+/-胎盘呈现更高的葡萄糖摄取和GLUT1和mTOR的更高的基因表达比VIP ^{+ / +}胎盘。然而，在缺乏 VIP 的母体环境中，无论胎儿胎盘基因型如何，胎盘摄取和经胎盘葡萄糖转运增加而胎儿体重不受影响。结果表明，正常背景下的 VIP 缺陷妊娠是合适的 FGR 模型，胎盘葡萄糖摄取和经胎盘转运增加。明显的代偿行为无法维持胎儿的正常生长，并可能导致以后的生活出现并发症。