Viral ssRNA induces first trimester trophoblast apoptosis through an inflammatory mechanism.
OBJECTIVE
Infection during pregnancy represents a significant cause of mobility and mortality. While viruses pose a major threat, little is known about their effect on early pregnancy, or the mechanisms involved. The objective of this study was to characterize the trophoblast response following exposure to viral ssRNA.


METHODS
First trimester trophoblast cells were treated with or without viral ssRNA. Cytokine production was measured using multiplex analysis and ELISA. Apoptosis was determined using Hoechst staining, cell viability, and caspase activity assays.


RESULTS
Treatment of trophoblasts with viral ssRNA increased their secretion of IL-8, IL-6, and IFNbeta. However, the ssRNA also induced trophoblast apoptosis. To test whether the viral ssRNA-induced inflammatory response was responsible for this induction of apoptosis, conditioned media (CM) from trophoblasts were added to a fresh culture of cells. The CM from viral ssRNA-treated induced higher levels of trophoblast apoptosis than the control CM. Moreover, recombinant IFNbeta induced trophoblast apoptosis.


CONCLUSIONS
We demonstrate that viral ssRNA induces a pro-inflammatory and type I interferon response in the trophoblast and this inflammatory process may indirectly induce trophoblast apoptosis. These results provide a novel mechanism by which certain viral infections might compromise placental integrity and function, and therefore, pregnancy outcome.
Aldo
Paulomi B
PB
Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University, School of Medicine, New Haven, CT 06510, USA.
Mulla
Melissa J
MJ
Romero
Roberto
R
Mor
Gil
G
Abrahams
Vikki M
VM
D017209:Apoptosis; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D057075:Enzyme Assays; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000276:immunology*; D012367:RNA, Viral / Q000494:pharmacology*; D014327:Trophoblasts / Q000166:cytology / Q000201:enzymology / Q000276:immunology*
D016207:Cytokines; D018836:Inflammation Mediators; D012367:RNA, Viral; D020169:Caspases