title: Umbilical cord gene expression reveals the molecular architecture of the fetal inflammatory response in extremely preterm newborns.
abstract: BACKGROUND
  The fetal inflammatory response (FIR) in placental membranes to an intrauterine infection often precedes premature birth raising neonatal mortality and morbidity. However, the precise molecular events behind FIR still remain largely unknown, and little has been investigated at gene expression level.
  
  
  METHODS
  We collected publicly available microarray expression data profiling umbilical cord (UC) tissue derived from the cohort of extremely low gestational age newborns (ELGANs) and interrogate them for differentially expressed (DE) genes between FIR and non-FIR-affected ELGANs.
  
  
  RESULTS
  We found a broad and complex FIR UC gene expression signature, changing up to 19% (3,896/20,155) of all human genes at 1% false discovery rate. Significant changes of a minimum 50% magnitude (1,097/3,896) affect the upregulation of many inflammatory pathways and molecules, such as cytokines, toll-like receptors, and calgranulins. Remarkably, they also include the downregulation of neurodevelopmental pathways and genes, such as Fragile-X mental retardation 1 (FMR1), contactin 1 (CNTN1), and adenomatous polyposis coli (APC).
  
  
  CONCLUSIONS
  The FIR expression signature in UC tissue contains molecular clues about signaling pathways that trigger FIR, and it is consistent with an acute inflammatory response by fetal innate and adaptive immune systems, which participate in the pathogenesis of neonatal brain damage.
authors.affiliation: Department of Pediatrics, Hospital de Figueres, Figueres, Spain.
authors.forename: Daniel
authors.identifier: http://orcid.org/0000-0002-5284-557X
authors.initials: D
authors.lastname: Costa
authors.affiliation: Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.|Research Program on Biomedical Informatics, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
authors.forename: Robert
authors.identifier: http://orcid.org/0000-0003-2229-4508
authors.initials: R
authors.lastname: Castelo
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D015331:Cohort Studies; D058967:Contactin 1 / Q000235:genetics; D005189:False Positive Reactions; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005865:Gestational Age; D006801:Humans; D007107:Immune System; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D014470:Umbilical Cord / Q000378:metabolism*
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D058967:Contactin 1; D051860:Fragile X Messenger Ribonucleoprotein 1; C555337:APC protein, human; C548669:CNTN1 protein, human; C497683:FMR1 protein, human