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16 November 2017 Group B streptococcus activates transcriptomic pathways related to premature birth in human extraplacental membranes in vitro
Hae-Ryung Park, Sean M. Harris, Erica Boldenow, Richard C. McEachin, Maureen Sartor, Mark Chames, Rita Loch-Caruso
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Abstract

Streptococcus agalactiae (group B streptococcus [GBS]) infection in pregnant women is the leading cause of infectious neonatal morbidity and mortality in the United States. Although inflammation during infection has been associated with preterm birth, the contribution of GBS to preterm birth is less certain. Moreover, the early mechanisms by which GBS interacts with the gestational tissue to affect adverse pregnancy outcomes are poorly understood. We hypothesized that short-term GBS inoculation activates pathways related to inflammation and premature birth in human extraplacental membranes. We tested this hypothesis using GBS-inoculated human extraplacental membranes in vitro. In agreement with our hypothesis, a microarray-based transcriptomics analysis of gene expression changes in GBS-inoculated membranes revealed that GBS activated pathways related to inflammation and preterm birth with significant gene expression changes occurring as early as 4 h postinoculation. In addition, pathways related to DNA replication and repair were downregulated with GBS treatment. Conclusions based on our transcriptomics data were further supported by responses of prostaglandin E2 (PGE2), and matrix metalloproteinases 1 (MMP1) and 3 (MMP3), all of which are known to be involved in parturition and premature rupture of membranes. These results support our initial hypothesis and provide new information on molecular targets of GBS infection in human extraplacental membranes.

Summary Sentence

Group B Streptococcus (GBS) activates premature birth and inflammation pathways in human extraplacental membranes in vitro, providing insight into early molecular responses underpinning GBS contributions to adverse birth outcomes.

© The Author(s) 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Hae-Ryung Park, Sean M. Harris, Erica Boldenow, Richard C. McEachin, Maureen Sartor, Mark Chames, and Rita Loch-Caruso "Group B streptococcus activates transcriptomic pathways related to premature birth in human extraplacental membranes in vitro," Biology of Reproduction 98(3), 396-407, (16 November 2017). https://doi.org/10.1093/biolre/iox147
Received: 7 June 2017; Accepted: 14 November 2017; Published: 16 November 2017
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