Novel insights into molecular mechanisms of abruption-induced preterm birth

Abstract

Preterm birth (PTB) complicates more than 12% of all deliveries. Despite significant research, the aetiology of most cases of PTB remains elusive. Two major antecedents of PTB, intra-amniotic infection and decidual haemorrhage (abruption), can exhibit dissimilar demographic and genetic predispositions, despite sharing common molecular and cellular pathways. The use of high-throughput, high-dimensional technologies reveals substantial crosstalk between the coagulation and inflammation pathways. Tissue factor, thrombin and cytokines are key mediators of this crosstalk. Abruptions are associated with excess thrombin generated from decidual-cell-expressed tissue factor. Although thrombin is a primary mediator of the coagulation cascade, it can also promote inflammation-associated PTB by enhancing expression of matrix metalloproteinase and neutrophil-chemoattracting and -activating chemokines. Here, we provide novel insights into the molecular mechanisms and pathways leading to PTB in the setting of placental abruption.

Activation of AMPK in human fetal membranes alleviates infection-induced expression of pro-inflammatory and pro-labour mediators

“…The many genetic and environmental factors that are implicated in contributing to spontaneous preterm labour, such as decidual senescence, uterine distention, and infection, are associated with increased inflammation [48]. Indicated preterm birth in the absence of labour in this study were due to reasons such as APH and placental abruption, which are also closely associated with inflammation [49]. These inflammatory conditions may decrease AMPK activity and thus could be a reason as to why we saw no additional effect of spontaneous preterm labour on AMPK activity.…”

Prevention of preterm birth: Harnessing science to address the global epidemic

“…Activation of the coagulation cascade that releases thrombin and other proteases may be initiated by decidual tissue factor, which can be released by infection, inflammation, hypoxia, or oxidative stress (67). In addition to thrombin, other proteases, such as elastase, may be involved in contraction signals, releasing fibronectin and promoting the breakdown of the chorion-decidual fusion (68).…”

Proteomics/diagnosis of chorioamnionitis and of relationships with the fetal exposome

“…5 In addition, although chorioamnionitis most often results from intra-amniotic infection, not all intrauterine inflammatory processes are caused by microbes and vice-versa. 6,7 It is critical to recognize that culture techniques identify only a fraction of micro-organisms implicated as etiological agents of chorioamnionitis. 8 Therefore, nuances in medical terminology with respect to clinical versus histological chorioamnionitis are important when choosing the ‘gold standard’ for either infection or inflammation.…”