Vasoactive intestinal peptide shapes first-trimester placenta trophoblast, vascular, and immune cell cooperation.

Autor: Paparini DE; IQUIBICEN-CONICET, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina.; Maternal and Fetal Health Research Centre, University of Manchester, Manchester Academic Health Science Centre, St. Mary's Hospital, Manchester, UK., Choudhury RH; Maternal and Fetal Health Research Centre, University of Manchester, Manchester Academic Health Science Centre, St. Mary's Hospital, Manchester, UK., Vota DM; IQUIBICEN-CONICET, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina., Karolczak-Bayatti M; Maternal and Fetal Health Research Centre, University of Manchester, Manchester Academic Health Science Centre, St. Mary's Hospital, Manchester, UK., Finn-Sell S; Maternal and Fetal Health Research Centre, University of Manchester, Manchester Academic Health Science Centre, St. Mary's Hospital, Manchester, UK., Grasso EN; IQUIBICEN-CONICET, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina., Hauk VC; IQUIBICEN-CONICET, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina., Ramhorst R; IQUIBICEN-CONICET, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina., Pérez Leirós C; IQUIBICEN-CONICET, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina., Aplin JD; Maternal and Fetal Health Research Centre, University of Manchester, Manchester Academic Health Science Centre, St. Mary's Hospital, Manchester, UK.
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 2019 Apr; Vol. 176 (7), pp. 964-980. Date of Electronic Publication: 2019 Mar 18.
DOI: 10.1111/bph.14609
Abstrakt: Background and Purpose: Extravillous trophoblast (EVT) cells 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 EVT outgrowth, spiral artery remodelling, balancing angiogenesis, and maintenance of immune homeostasis.
Experimental Approach: First-trimester placental tissue (five to nine weeks of gestation) was collected, and was used for EVT outgrowth experiments, immunofluorescence, isolation of decidual natural killer (dNK) cells and decidual macrophages (dMA), and functional assays. Peripheral blood monocytes were differentiated 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 macrophages.
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.
(© 2019 The British Pharmacological Society.)
Databáze: MEDLINE
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