VIP modulates glucose uptake by trophoblast cells and is involved in murine fetal growth

FÁTIMA MERECH; GUILLERMINA CALO; JAMES WASCHEK; DAIANA MARINA VOTA; DANIEL PAPARINI; ROSANNA RAMHORST; VANESA HAUK; LUCILA GALLINO; CLAUDIA PÉREZ LEIRÓS

Manchester

Congreso; International Federation of Placenta Associations Meeting; 2017

International Federation of Placenta Associations

The transport of nutrients across the placenta is strictly regulated and deficiencies in this process are associated to intrauterine growth restriction among other complications. Glucose is the major energy substrate for the placenta and fetus. Its transfer to the fetus is regulated by maternal levels, placental glucose metabolism and facilitated transport through Glut carrier proteins. Glut 1 appears to be the primary carrier and is found at both the maternal and the fetal-facing of trophoblast membranes. The vasoactive intestinal peptide (VIP) is a pleiotropic neuropeptide that was shown to inhibit glucose oxidation in rat enterocytes. We have previously demonstrated that VIP is synthesized by human trophoblast cells and favors trophoblast cell migration and invasion, two main processes required for placentation. Objectives: To study the impact of trophoblast VIP deficiency in the regulation of glucose uptake by trophoblast cells, placenta weight and fetal growth. Methods: Two approaches were used, a VIP knocked-down human first trimester trophoblast cell line, Swan-71, and implantation sites of C57BL/6 WT females mated to VIP-/- or WT males. Swan-71 VIP knocking-down was carried out using a VIP siRNA. GLUT1 and mTOR expression were evaluated by qRT-PCR, glucose uptake by flow cytometry or fluorometry using the fluorescent analogue 2-NBDG. Results: An increase of GLUT1 and mTOR expression in siVIP vs. scramble transfected Tb cells as well as an increment of glucose uptake were observed. On the other hand, VIP deficient embryos showed reduced weight (WTxWT vs. WTxKO, p