title: Trophoblast-induced changes in C-x-C motif chemokine 10 expression contribute to vascular smooth muscle cell dedifferentiation during spiral artery remodeling.
abstract: OBJECTIVE
  During pregnancy, fetal trophoblast disrupt endothelial cell and vascular smooth muscle cell (VSMC) interactions in spiral arteries of the maternal decidua to enable increased nutritional and oxygen delivery to the fetus. Little is known regarding this transformation because of difficulties of studying human pregnancy in vivo. This study investigated how trophoblast-secreted factors affect the interactions of vascular cells and the differentiation status of VSMC during spiral arteries remodeling using 3-dimensional vascular spheroid coculture.
  
  
  RESULTS
  Endothelial cell and VSMC were cocultured in hanging droplets to form spheroids representing an inverted vessel lumen. Control or conditioned media from an extravillous trophoblast (EVT) cell line was incubated with vascular spheroids for 24 hours. Spheroid RNA was then analyzed by Illumina Sentrix BeadChip array. Spheroids incubated with EVT conditioned medium showed significant up/downregulation of 101 genes (>1.5-fold; P<0.05), including an upregulation of C-X-C motif chemokine 10 (IP-10). C-X-C motif chemokine 10 expression was confirmed by qualitative real-time PCR and Western blot analysis of spheroids, and immunohistochemistry of first trimester decidua and ex vivo dissected nonplacental bed spiral arteries. EVT conditioned medium reduced VSMC expression of differentiation markers, and both EVT conditioned medium and C-X-C motif chemokine 10 increased motility of VSMC indicating dedifferentiation of VSMC.
  
  
  CONCLUSIONS
  EVT-induced C-X-C motif chemokine 10 expression may contribute to spiral arteries remodeling during pregnancy by altering the motility and differentiation status of the VSMC in the vessel.
authors.affiliation: Division of Biomedical Sciences, Reproductive and Cardiovascular Disease Research Group, St George's University of London, United Kingdom.
authors.forename: Alison E
authors.initials: AE
authors.lastname: Wallace
authors.forename: Judith E
authors.initials: JE
authors.lastname: Cartwright
authors.forename: Runa
authors.initials: R
authors.lastname: Begum
authors.forename: Ken
authors.initials: K
authors.lastname: Laing
authors.forename: Baskaran
authors.initials: B
authors.lastname: Thilaganathan
authors.forename: Guy S
authors.initials: GS
authors.lastname: Whitley
mesh_terms: D001158:Arteries / Q000378:metabolism; D015153:Blotting, Western; D054337:Cell Dedifferentiation / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D003656:Decidua / Q000098:blood supply*; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D019899:Paracrine Communication; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018874:Spheroids, Cellular; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D017077:Culture Media, Conditioned; D007371:Interferon-gamma