BACKGROUND AND PURPOSE: Extravillous trophoblast cells (EVT) are responsible for decidual stromal invasion, vascular transformation and the recruitment and functional modulation of maternal leukocytes in the first trimester pregnant uterus. An early disruption of EVT function leads to placental insufficiency underlying pregnancy complications such as preeclampsia and fetal growth restriction. Vasoactive intestinal peptide (VIP) is a vasodilating and immune modulatory factor synthesized by trophoblast cells. However, its role in first trimester placenta has not been explored. Here we tested the hypothesis that VIP is involved in first trimester extravillous trophoblast outgrowth, spiral artery remodelling, balancing angiogenesis and maintenance of immune homeostasis.
EXPERIMENTAL APPROACH: First trimester placental tissue (5-9 wk gestation) (n=31) was collected and it was used for EVT outgrowths experiments, immunofluorescence, isolation of decidual NK cells (dNK) and macrophages (dMA) and functional assays. Peripheral blood monocytes were differenciated with GM-CSF and used for angiogenesis assays.
KEY RESULTS: In decidua basalis, VIP+ EVT were observed sprouting from cell columns and lining spiral arterioles. EVT migrating from placental explants were also VIP+. VIP increased EVT outgrowth and IL-10 release, whereas it decreased pro-inflammatory cytokine production in EVT, dNK cells and dMA. VIP disrupted endothelial cell networks, both directly and indirectly via an effect on MA.
CONCLUSION AND IMPLICATIONS: The results suggest that VIP assists the progress of EVT invasion and vessel remodelling in first trimester placental bed in an immunologically 'silent' milieu. The effects of VIP in the present ex vivo human placental model endorse its potential as a therapeutic candidate for deep placentation disorders.
|Journal||British Journal of Pharmacology|
|Early online date||6 Feb 2019|
|Publication status||Published - 2019|