TROPHOBLAST VIP-DEFICIENCY ENTAILS IMMUNE HOMEOSTASIS LOSS AND ADVERSE PREGNANCY OUTCOME IN MICE

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

FASEB JOURNAL

FEDERATION AMER SOC EXP BIOL

Lugar: Bethesda; Año: 2018

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 maternalarteries and the functional shaping of decidual leukocyte populations. Insufficient trophoblast invasion,inadequate vascular remodeling and a loss of immunological homeostasis are associated with pregnancycomplications, such as preeclampsia and intrauterine growth restriction. Vasoactive intestinal peptide is apleiotropic neuropeptide synthetized in trophoblasts at the maternal-placental interface. It regulates thefunction of trophoblast cells and their interaction with decidual leukocytes. By means of a murine modelof pregnancy in normal maternal background with VIP-deficient trophoblast cells, here we demonstratethat trophoblast VIP is critical for trophoblast function: VIP gene haploinsufficiency results in lowerMMP9 expression, reduced migration and invasion capacities. A reduced number of regulatory T cells atthe implantation sites along with a lower expression of proangiogenic and antiinflammatory markers werealso observed. Findings detected in the implantation sites at early stages were followed by an abnormalplacental structure and lower fetal weight. This effect was overcome by VIP treatment to the earlypregnant mice. Our results support the relevance of trophoblast-synthesized VIP as a critical factor in vivofor trophoblast cell function and immune homeostasis maintenance in mouse pregnancy.