RNA Sequencing Reveals Distinct Immune Responses in the Chorioamniotic Membranes of Women with Preterm Labor and Microbial or Sterile Intra-Amniotic Inflammation

Preterm birth can occur in the context of an inflammatory response in the amniotic cavity, either driven by microbes (i.e., intra-amniotic infection) or in the absence of detectable microorganisms (i.e., sterile intra-amniotic inflammation). Each condition triggers immune responses that have deleterious effects on neonatal life; yet, the extent of such immune responses in the fetal membranes (fetal tissues surrounding the amniotic cavity) is poorly understood. To fill this gap in knowledge, PRB researchers applied RNA sequencing and systems immunobiology approaches to investigate the transcriptome of the fetal membranes in the context of intra-amniotic infection or sterile intra-amniotic inflammation.

The team reported that the sterile or microbial nature of intra-amniotic inflammation was associated with distinct transcriptomic profiles in the fetal membranes. Notably, such differences involved host response to pathogens in the fetal membranes of women with intra-amniotic infection compared to those from women without inflammation. Moreover, the immune response in the fetal membranes of women with sterile intra-amniotic inflammation was milder than that induced by microbes and involved the upregulation of alarmins and inflammasome-related molecules. Lastly, the presence of maternal or fetal inflammatory responses in the placenta was associated with the enhanced upregulation of immune processes in the fetal membranes. These findings provide insight into the immune responses against microbes or alarmins that take place in the fetal tissues surrounding the amniotic cavity.

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