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

ABSTRACT

Preterm labor precedes premature birth, the leading cause of neonatal morbidity and mortality worldwide. Preterm labor can occur in the context of either microbe-associated intra-amniotic inflammation (i.e., intra-amniotic infection) or intra-amniotic inflammation in the absence of detectable microorganisms (i.e., sterile intra-amniotic inflammation). Both intra-amniotic infection and sterile intra-amniotic inflammation trigger local immune responses that have deleterious effects on fetal life. Yet, the extent of such immune responses in the fetal tissues surrounding the amniotic cavity (i.e., the chorioamniotic membranes) is poorly understood. By using RNA sequencing (RNA seq) as a discovery approach, we found that there were significant transcriptomic differences involving host response to pathogens in the chorioamniotic membranes of women with intra-amniotic infection compared to those from women without inflammation. In addition, the sterile or microbial nature of intra-amniotic inflammation was associated with distinct transcriptomic profiles in the chorioamniotic membranes. Moreover, the immune response in the chorioamniotic membranes of women with sterile intra-amniotic inflammation was milder in nature than that induced by microbes and involved the upregulation of alarmins and inflammasome-related molecules. Lastly, the presence of maternal and fetal inflammatory responses in the placenta was associated with the upregulation of immune processes in the chorioamniotic membranes. Collectively, these findings provide insight into the immune responses against microbes or alarmins that take place in the fetal tissues surrounding the amniotic cavity, shedding light on the immunobiology of preterm labor and birth.