Transcriptomic Profiling of Human Choriodecidua During Term Labor: Inflammation as a Key Driver of Labor

Stephen, Gillian; Liu, Sylvia; Hamilton, Sarah; Tower, Clare; Harris, Lynda K.; Stevens, Adam; Jones, Rebecca L.

doi:10.1111/aji.12328

Cited by 51 publications

(54 citation statements)

References 51 publications

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“…Interestingly, sterile inflammation has been suggested to induce a common inflammatory pathway leading to labor at term in normal pregnancies (Kobayashi 2012, Phillippe 2014. Accordingly, transcriptomic analysis of choriodecidual tissue collected at term predicted HMGB1 as a potential upstream regulator of parturition (Stephen et al 2015). As mentioned previously, cffDNA is another alarmin candidate initiator of labor at term (Phillippe 2014).…”

Section: Preterm Labormentioning

confidence: 76%

“…Furthermore, HMGB1 administration ex vivo in human fetal membranes induces p38-mediated IL-6 and IL-8 production (Bredeson et al 2014). In this setting, a potential role in labor for the HMGB1 pathway was reported using transcriptomics and bioinformatics analysis (Stephen et al 2015, Menon et al 2016. Additionally, HMGB1 and its receptors RAGE, TLR2 and TLR4 are found in cervix and extranuclear fraction of HMGB1 increases with labor onset at term and preterm (Dubicke et al 2010), suggesting that HMGB1 may play a role in cervical ripening.…”

Section: Preterm Labormentioning

confidence: 99%

See 1 more Smart Citation

Sterile inflammation and pregnancy complications: a review

Nadeau-Vallée¹,

Obari²,

Palacios³

et al. 2016

Reproduction

219

161

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Inflammation is essential for successful embryo implantation, pregnancy maintenance and delivery. In the last decade, important advances have been made in regard to endogenous, and therefore non-infectious, initiators of inflammation, which can act through the same receptors as pathogens. These molecules are referred to as damage-associated molecular patterns (DAMPs), and their involvement in reproduction has only recently been unraveled. Even though inflammation is necessary for successful reproduction, untimely activation of inflammatory processes can have devastating effect on pregnancy outcomes. Many DAMPs, such as uric acid, high-mobility group box 1 (HMGB1), interleukin (IL)-1 and cell-free fetal DNA, have been associated with pregnancy complications, such as miscarriages, preeclampsia and preterm birth in preclinical models and in humans. However, the specific contribution of alarmins to these conditions is still under debate, as currently there is lack of information on their mechanism of action. In this review, we discuss the role of sterile inflammation in reproduction, including early implantation and pregnancy complications. Particularly, we focus on major alarmins vastly implicated in numerous sterile inflammatory processes, such as uric acid, HMGB1, IL-1α and cell-free DNA (especially that of fetal origin) while giving an overview of the potential role of other candidate alarmins.Reproduction (2016) 152 R277-R292

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Section: Preterm Labormentioning

confidence: 76%

Section: Preterm Labormentioning

confidence: 99%

Sterile inflammation and pregnancy complications: a review

Nadeau-Vallée¹,

Obari²,

Palacios³

et al. 2016

Reproduction

219

161

View full text Add to dashboard Cite

show abstract

“…Indeed, DSCs are generated from ESCs in vitro through the use of medroxyprogesterone acetate (a nonmetabolizable progestin), frequently in combination with a cAMP analog and/or estrogen, whereas we found that the systemic hormonal environment of early pregnancy, which includes high P4 levels, is insufficient to induce H3K27me3 accrual in mouse ESCs in vivo, as discussed above. Second, it is possible that in vitro decidudecidual activation and term parturition in humans rather than inflammation, as currently thought (2,30,32). The actual nature of H3K27me3 dynamics in human DSCs in vivo remains to be determined, however, with 2 genome-wide studies to date showing that H3K27me3 levels remain relatively constant or decline slightly when ESCs are decidualized in vitro over a 1-to 2-week period (33,34).…”

Section: Discussionmentioning

confidence: 99%

H3K27me3 dynamics dictate evolving uterine states in pregnancy and parturition

Nancy¹,

Siewiera²,

Rizzuto³

et al. 2017

Journal of Clinical Investigation

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“…CXCR4 encodes a CXC chemokine receptor specific for stromal cell-derived factor-1. CXCR4 has been shown to be up regulated in labor and is related to inflammatory response(24). SDF1 needs CXCR4 as a receptor and it is “probable that the activation of CXCR4 by SDF1 is one of the sources of maternal-fetal immune tolerance”(25).…”

Section: Discussionmentioning

confidence: 99%

Structural and genomic variation in preterm birth

et al. 2016

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BackgroundRuns of homozygosity (ROH) are consecutive homozygous genotypes, which may result from population inbreeding or consanguineous marriages. ROH enhance the expression of recessive traits.MethodsWe mapped ROH in a case control study of women delivering at term compared to women delivering at or before 34 weeks gestation. Gene sets known to be important in risk of preterm birth were examined for their overlap with identified ROH segments.ResultsWhile we found no evidence of increased burden of ROH or copy number variations in mothers delivering at or before 34 weeks compared to term, we identified 424 genome-wide 50 kb segments with significant difference in abundance of overlapping ROH segments in cases versus controls, p<0.05. These regions overlap 199 known genes. We found preterm birth associated genes (CXCR4, MYLK, PAK1) and genes shown to have an evolutionary link to preterm (CXCR4, PPP3CB, C6orf57, DUSP13, and SLC25A45) with significant differences in abundance of overlapping ROH blocks in cases versus controls, p<0.001.ConclusionWe conclude, while we found no significant burden of runs of homozygosity, we did identify genomic regions with significantly greater abundance of ROH blocks in women delivering preterm that overlapped genes known to be involved in preterm birth.

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Transcriptomic Profiling of Human Choriodecidua During Term Labor: Inflammation as a Key Driver of Labor

Abstract: This study confirms inflammatory processes are major players in labor events in choriodecidua, as in other gestational tissues. Suppressing uterine inflammation is likely to be critical for arresting premature labor.

Cited by 51 publications

References 51 publications

Sterile inflammation and pregnancy complications: a review

Sterile inflammation and pregnancy complications: a review

H3K27me3 dynamics dictate evolving uterine states in pregnancy and parturition

Structural and genomic variation in preterm birth

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