title: Fetomaternal cross talk in the placental vascular bed: control of coagulation by trophoblast cells.
abstract: Humans and rodents exhibit a peculiar type of placentation in which zygote-derived trophoblast cells, rather than endothelial cells, line the terminal maternal vascular space. This peculiar aspect of the placental vasculature raises important questions about the relative contribution of fetal and maternal factors in the local control of hemostasis in the placenta and how these might determine the phenotypic expression of thrombophilia-associated complications of pregnancy. Using genomewide expression analysis, we identify a panel of genes that determine the ability of fetal trophoblast cells to regulate hemostasis at the fetomaternal interface. We show that spontaneous differentiation of trophoblast stem cells is associated with the acquisition of an endothelial cell-like thromboregulatory gene expression program. This program is developmentally regulated and conserved between mice and humans. We further show that trophoblast cells sense, via the expression of protease activated receptors, the presence of activated coagulation factors. Engagement of these receptors results in cell-type specific changes in gene expression. Our observations define candidate fetal genes that are potential risk modifiers of maternal thrombophilia-associated pregnancy complications and provide evidence that coagulation activation at the fetomaternal interface can affect trophoblast physiology altering placental function in the absence of frank thrombosis.
authors.affiliation: Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Sood
authors.forename: Shawn
authors.initials: S
authors.lastname: Kalloway
authors.forename: Alan E
authors.initials: AE
authors.lastname: Mast
authors.forename: Cecilia J
authors.initials: CJ
authors.lastname: Hillard
authors.forename: Hartmut
authors.initials: H
authors.lastname: Weiler
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D001779:Blood Coagulation Factors / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011247:Pregnancy / Q000502:physiology*; D011250:Pregnancy Complications, Hematologic / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D019851:Thrombophilia / Q000235:genetics / Q000378:metabolism; D013927:Thrombosis / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*; D015053:Zygote / Q000166:cytology / Q000502:physiology
chemical_list: D001779:Blood Coagulation Factors; D011956:Receptors, Cell Surface