Prostaglandin Metabolites and Human Labour

Date
2024-05-29
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Abstract
Preterm birth is a major cause of neonatal morbidity and mortality worldwide. The etiology of preterm birth, particularly those preterm births preceded by spontaneous preterm labour, is largely unknown. Prostaglandins and other lipid mediators in the eicosanoid family, have been implicated in the processes of term and preterm labour, although exactly which eicosanoids are involved and their exact roles in these processes has yet to be elucidated. To this end, we initially investigated the eicosanoid profile of discovery cohorts of maternal serum and urine. Analyses in first trimester serum revealed decreased levels of lipoxygenase pathway eicosanoids early in pregnancy in individuals with subsequent preterm birth. In 2nd and 3rd trimester urine, we found that term labour was associated with decreasing urinary tetranor prostaglandin metabolites (t-PGFM, t-PGEM, and t-PGDM), potentially suggesting altered prostaglandin metabolism with term labour. To interrogate the urine data further, we investigated levels of prostaglandin metabolites in a larger set of n=308 maternal urine samples and found that prostaglandin F2a and PGE2 metabolites (PGFM and PGEM, respectively) were increased with term labour, but unchanged leading up to labour onset. Finally, we investigated regulation of the prostaglandin metabolizing enzyme, 15-PGDH, by IL-1B and CRH and demonstrated that neither 15-PGDH levels nor PGE2 metabolism was significantly affected by either treatment in a chorionic explant model. In conclusion, eicosanoids and their metabolites appear to be involved in the labour process, although future work is required to determine the factors that regulate their production and metabolism and the utility of these lipid mediators as biomarkers for labour.
Description
Keywords
pregnancy, labour, preterm labour, eicosanoids, prostaglandins
Citation
Wood, E. (2024). Prostaglandin metabolites and human labour (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.