Cytomegalovirus infection of trophoblast cells elicits an inflammatory response: a possible mechanism of placental dysfunction.
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.
Chou
Doris
D
Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6142, USA. dchou@obgyn.upenn.edu
Ma
Yujie
Y
Zhang
Jian
J
McGrath
Cindy
C
Parry
Samuel
S
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*
D015850:Interleukin-6; D016209:Interleukin-8; D007770:L-Lactate Dehydrogenase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases