Transcriptome signature identifies distinct cervical pathways induced in lipopolysaccharide-mediated preterm birth

Alexandra R. Willcockson, Tulip Nandu, Cheuk Lun Liu, Shanmugasundaram Nallasamy, W. Lee Kraus, Mala Mahendroo

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

With half a million babies born preterm each year in the USA and about 15 million worldwide, preterm birth (PTB) remains a global health issue. Preterm birth is a primary cause of infant morbidity and mortality and can impact lives long past infancy. The fact that there are numerous, and many currently unidentified, etiologies of PTB has hindered development of tools for risk evaluation and preventative therapies. Infection is estimated to be involved in nearly 40% of PTBs of known etiology; therefore, understanding how infection-mediated inflammation alters the cervical milieu and leads to preterm tissue biomechanical changes are questions of interest. Using RNA-seq, we identified enrichment of components involved in inflammasome activation and unique proteases in the mouse cervix during lipopolysaccharide (LPS)-mediated PTB and not physiologically at term before labor. Despite transcriptional induction of inflammasome components, there was no evidence of functional activation based on assessment of mature IL1B and IL18 proteins. The increased transcription of proteases that target both elastic fibers and collagen and concentration of myeloid-derived cells capable of protease synthesis in the cervical stroma support the structural disruption of elastic fibers as a functional output of protease activity. The recent demonstration that elastic fibers contribute to the biomechanical function of the pregnant cervix suggests their protease-induced disruption in the infection model of LPS-mediated PTB and may contribute to premature loss of mechanical competency and preterm delivery. Collectively, the transcriptomics and ultrastructural data provide new insights into the distinct mechanisms of premature cervical remodeling in response to infection.

Original languageEnglish (US)
Pages (from-to)408-421
Number of pages14
JournalBiology of Reproduction
Volume98
Issue number3
DOIs
StatePublished - Mar 1 2018

Fingerprint

Premature Birth
Transcriptome
Lipopolysaccharides
Peptide Hydrolases
Elastic Tissue
Inflammasomes
Infection
Cervix Uteri
Interleukin-18
Infant Mortality
Myeloid Cells
Collagen
RNA
Inflammation
Morbidity
Proteins

Keywords

  • Cervix
  • Cytokines
  • Elastic fibers
  • Extracellular matrix
  • Inflammation
  • Preterm birth
  • Proteases

ASJC Scopus subject areas

  • Cell Biology

Cite this

Transcriptome signature identifies distinct cervical pathways induced in lipopolysaccharide-mediated preterm birth. / Willcockson, Alexandra R.; Nandu, Tulip; Liu, Cheuk Lun; Nallasamy, Shanmugasundaram; Kraus, W. Lee; Mahendroo, Mala.

In: Biology of Reproduction, Vol. 98, No. 3, 01.03.2018, p. 408-421.

Research output: Contribution to journalArticle

Willcockson, Alexandra R. ; Nandu, Tulip ; Liu, Cheuk Lun ; Nallasamy, Shanmugasundaram ; Kraus, W. Lee ; Mahendroo, Mala. / Transcriptome signature identifies distinct cervical pathways induced in lipopolysaccharide-mediated preterm birth. In: Biology of Reproduction. 2018 ; Vol. 98, No. 3. pp. 408-421.
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