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Understanding the mechanisms of human labour to improve management of preterm labour and induction of labour


Bristol Medical School

, Applications accepted all year round Self-Funded PhD Students Only

About the Project

Parturition, or labour, is essential for mammalian existence. However, despite decades of research, the mechanism for human labour is poorly understood. This is partly because animal models do not reliably reflect what happens in humans, and it has previously been difficult to perform experiments on human pregnancies. This incomplete understanding limits our ability to manage complications of labour such as preterm labour and induction of labour (1-3). We have utilised metabolomic and phosphoproteomic techniques to investigate changes in maternal and cord plasma metabolites and myometrial phosphoproteins associated with labour and delivery in humans (4). The results of these studies have given us novel insights into signalling pathways involving the fetus, placenta and myometrium during spontaneous labour. These findings have provided new avenues of research and identified potential new therapeutic targets to enable better management of preterm labour and/or induction of labour.

The overarching theme of this PhD would be to further develop this exciting work, including investigation of the functional role of the myometrial phosphoproteins identified as being important for normal labour in human parturition, and to investigate further the identified signalling pathways.

Methods would include myo-bath studies of human myometrium and metabolomic analysis of maternal and cord blood.

References

1. Ratajczak CK, Muglia LJ. Insights into parturition biology from genetically altered mice. Pediatr Res 2008;64(6):581-9. doi: 10.1203/PDR.0b013e31818718d2 [published Online First: 2008/08/06]

2. Lopez Bernal A. Overview. Preterm labour: mechanisms and management. BMC Pregnancy Childbirth 2007;7 Suppl 1:S2. doi: 10.1186/1471-2393-7-s1-s2 [published Online First: 2007/06/19]

3. Sharp GC, Hutchinson JL, Hibbert N, et al. Transcription Analysis of the Myometrium of Labouring and Non-Labouring Women. PloS one 2016;11(5):e0155413-e13. doi: 10.1371/journal.pone.0155413

4. Birchenall KA, Welsh GI, Lopez Bernal A. Metabolite Changes in Maternal and Fetal Plasma Following Spontaneous Labour at Term in Humans Using Untargeted Metabolomics Analysis: A Pilot Study. Int J Environ Res Public Health 2019;16(9) doi: 10.3390/ijerph16091527 [published Online First: 2019/05/06]

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