Immunology of choriodecidua and onset of labour

Abstract

Introduction: Labour is a well-orchestrated process associated with inflammation; its onset is a poorly understood retrospective diagnosis. Immunology of pregnancy and labour is an area of wide interest; however, knowledge is lacking in what occurs at the maternal-fetal interface, the decidua. The aim of this thesis was to better understand the role of decidual immune cells in preterm birth and term labour while associating metabolites with immune cells that may be pivotal in labour. Methodology: Multiple cytokine assays were used to quantify cytokines/chemokines in choriodecidua/placenta. Flow cytometry was used to identify immune cells in decidua, placenta, maternal and cord blood. Mass spectrometry was used to quantify urinary metabolites. Results: Study one showed that choriodecidua was the most inflammatory gestational tissue analysed. Cytokines/chemokines indicated that NK cells, monocytes, T cells and neutrophils may play a significant role in preterm birth. Increased IL-8 in choriodecidua was associated with worse neonatal outcomes. Study two revealed a shift from predominantly CD56bright NK cells to a predominant subset of CD56+CD16+ NK cells with onset of term labour in decidua. Decidual NKbright cells and Tregs work together to maintain uterine quiescence at term, which is lost with labour. CD4+ Tregs and CD8+ Tregs were significantly higher in decidua than placenta/blood at term. Decidual monocytes, T cells and neutrophils did not alter with the onset of labour. Study three did not identify a signature urinary metabolic profile that is associated with the onset of labour. It highlighted that factors such as diet and lifestyle may cause inter-personal variability.

Conclusions: This thesis highlights that the tolerant immune cells and their interaction with cytokines/chemokines maintain an immunological equilibrium in the decidua. This is altered with the onset of labour. Urinary metabolites inconsistently altered with the onset of labour, there was no signature urinary metabolic profile associated with labour.