VIP-deficient mice pregnancy exhibit growth impairment, increased placental glucose uptake and altered transplacental transport

MERECH, FÁTIMA; HAUK, VANESA; PAPARINI, DANIEL; NAGUILA, ZAIRA; RAMHORST, ROSANNA; WASCHEK, JAMES; PÉREZ LEIRÓS, CLAUDIA; VOTA, DAIANA

Simposio; International Symposium of Reproductive Health; 2021

Background: Glucose uptake by the placenta and transplacental transport are finely regulated processes required for placental and fetal development. Deficient placentation is associated with pregnancy complications such as preeclampsia and fetal growth restriction as well as fetal programming for diseases in adult life. The vasoactive intestinal peptide (VIP) has embryotrophic effects in mice and regulates human cytotrophoblast function and metabolism. Objective: Our aim was to evaluate the in vivo placental glucose uptake and transfer to the fetus in WT or VIP-deficient placentas and we investigated the role of endogenous VIP in the regulation of placental glucose and amino acid uptake. Design: Wild type C57BL/6 (WT) females were mated with WT or VIP knock-out (VIP KO) males. Glucose uptake and transplacental transport were evaluated by the injection of 3mM D-glucose analogue 2-NBDG in pregnant mice at gestational day 17.5. Placental gene expression was measured by RT-qPCR. For ex vivo experiments, VIP+/+ placental explants were incubated with 100nM VIP antagonist prior to the addition of 2-NBDG or 14C-MeAIB to evaluate glucose and amino acid uptake, respectively. Results: Placental weight was unaltered due to placental VIP deficiency, whereas embryonic growth was impaired. Paradoxically, VIP+/- placentas presented with higher glucose uptake and GLUT1/mTOR gene expression compared with VIP+/+ placentas (p