Trophoblast VIP deficiency entails immune homeostasis loss and adverse pregnancy outcome in mice

HAUK, VANESA; VOTA, DAIANA; GALLINO, LUCILA; CALO, GUILLERMINA; PAPARINI, DANIEL; MERECH, FÁTIMA; OCHOA, FEDERICO; ZOTTA, ELSA; RAMHORST, ROSANNA; WASCHEK, JAMES; LEIRÓS, CLAUDIA PÉREZ

FASEB JOURNAL

FEDERATION AMER SOC EXP BIOL

Lugar: Bethesda; Año: 2019 vol. 33 p. 1801 - 1810

0892-6638

Immune homeostasis maintenance throughout pregnancy is critical for normal fetal development.Trophoblast cells differentiate into an invasive phenotype and contribute to the transformation of maternal arteriesand the functional shaping of decidual leukocyte populations. Insufficient trophoblast invasion, inadequate vascularremodeling, and a loss of immunologic homeostasis are associated with pregnancy complications, such aspreeclampsia and intrauterine growth restriction. Vasoactive intestinal peptide (VIP) is a pleiotropic neuropeptidesynthetized in trophoblasts at the maternal?placental interface. It regulates the function of trophoblast cells andtheir interaction with decidual leukocytes. By means of a murine model of pregnancy in normal maternal backgroundwith VIP-deficient trophoblast cells, here we demonstrate that trophoblast VIP is critical for trophoblastfunction: VIP gene haploinsufficiency results in lower matrix metalloproteinase 9 expression, and reduced migrationand invasion capacities. A reduced number of regulatory T cells at the implantation sites along with a lowerexpression of proangiogenic and antiinflammatory markers were also observed. Findings detected in the implantationsites at early stages were followed by an abnormal placental structure and lower fetal weight. This effect wasovercome by VIP treatment of the early pregnant mice. Our results support the relevance of trophoblast-synthesizedVIP as a critical factor in vivo for trophoblast-cell function and immune homeostasis maintenance in mousepregnancy.?Hauk, V., Vota, D., Gallino, L., Calo, G., Paparini, D., Merech, F., Ochoa, F., Zotta, E., Ramhorst, R.,Waschek, J., Leiros, C. P. Trophoblast VIP deficiency entails immune homeostasis loss and adverse pregnancy ´outcome in mice.