Investigating the trigger for human parturition using metabolomic and phosphoproteomic techniques within case-control and cohort studies

Abstract

The mechanism for human labour remains poorly understood, restricted by difficulties in human pregnancy experimentation, and this limits our ability to manage complications of parturition including spontaneous preterm birth and induction of labour. The studies presented in this thesis utilise metabolomic and phosphoproteomic techniques to improve our understanding of the pathways involved in the trigger for labour in humans.
The first study in the thesis compared mass spectrometry metabolomics analysis of maternal and cord plasma at the time of delivery, and the results indicate that the trigger for spontaneous labour in humans may involve endocannabinoid, sphingolipid and ceramide pathways. The second study presented investigates this further, comparing the metabolic profiles of maternal, cord artery, and cord vein blood sampled from women during low-risk pregnancies, including comparisons of metabolite concentrations between different labour onsets and delivery. This study indicates that there are inherent differences in fetal and maternal signals between women who spontaneously labour and women who have an induction of labour. The third study assessed potential associations between the maternal metabolic profile measured in the second trimester with gestational age at delivery within the Born in Bradford cohort study (analysis sample n = 7440). This study indicates a metabolic profile of dyslipidaemia may be associated with shorter gestational age at delivery, and that non-pathological human labour may involve pathways related to inflammation and vascular function. The final study used phosphoproteomics analysis of fresh myometrium in vitro, and the findings indicate that there may be a myometrial phenotype associated with failed induction of labour and failure to progress.
Taken together, these results provide novel leads to follow in order to progress our quest for a full understanding of the trigger for spontaneous labour in humans.

Date of Award	23 Mar 2021
Original language	English
Awarding Institution	University of Bristol
Supervisor	Andres Lopez Bernal (Supervisor), Debbie A Lawlor (Supervisor), Gavin I Welsh (Supervisor) & Maria C Borges (Supervisor)