title: Cytomegalovirus infection of trophoblast cells elicits an inflammatory response: a possible mechanism of placental dysfunction.
abstract: OBJECTIVE
  We sought to determine whether cytomegalovirus infection of extravillous trophoblast cells induces inflammatory changes that lead to cell death.
  
  
  METHODS
  Extravillous trophoblast (HTR-8/SVneo) cells were infected with cytomegalovirus. Cell death assays were performed 8 to 48 hours after infection. The expression and secretion of cytokines (interleukin-6 and -8) preceding cell death was measured by polymerase chain reaction and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Cell viability (lactate dehydrogenase assay) was reduced approximately 20%, and rates of apoptosis (measured by TdT-mediated dUTP-X nick end labeling [TUNEL] assay) were increased approximately 40% at 16 to 48 hours after infection. Significantly elevated levels of caspase-3 mRNA levels were observed before increased cell death. Interleukin-6 and -8 mRNA expression and protein secretion were up-regulated 8 to 16 hours after cytomegalovirus infection.
  
  
  CONCLUSIONS
  Placental exposure to cytomegalovirus induces an inflammatory response that precedes invasive trophoblast cell death. Cytomegalovirus may prevent normal placental invasion, which results in adverse reproductive outcomes that are associated with placental dysfunction.
authors.affiliation: Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6142, USA. dchou@obgyn.upenn.edu
authors.forename: Doris
authors.initials: D
authors.lastname: Chou
authors.forename: Yujie
authors.initials: Y
authors.lastname: Ma
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Cindy
authors.initials: C
authors.lastname: McGrath
authors.forename: Samuel
authors.initials: S
authors.lastname: Parry
mesh_terms: D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival; D003586:Cytomegalovirus Infections / Q000378:metabolism*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology / Q000821:virology*
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D007770:L-Lactate Dehydrogenase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases