Reproduction Abstracts

Mass spectrometry methods enable the detection of metabolite profiles in clinical samples, facilitating the assessment of maternal physiological changes on the molecular level associated with pregnancy. Notably, lipid metabolites hold significant importance across diverse conditions, especially in relation to inflammation and the immune response, although their exploration in the context of Hyperemesis Gravidarum (HG) is limited.^1-3 The purpose was to establish a non-invasive urine analysis for bioactive lipid metabolites – oxylipins, including prostaglandins and related compounds, thereby facilitating investigations of HG-dependent physiological changes in relation to nausea and vomiting during pregnancy. A targeted liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method was optimized and validated with regard to clinically relevant lipid metabolites in urine. Sample preparation protocols were developed based on solid phase extraction (SPE) and dispersive solid phase extraction (dSPE) using HKUST-1 metal organic framework material for isolation and concentration of oxylipins under study. LC-MS/MS method performance was assessed by native and isotopically labelled standards for recovery rates, matrix effects, accuracy, precision, limit-of-quantification and limit-of-detection. The resulting method satisfied the validation criteria and was successfully applied to urine. The pathophysiology of HG remains incompletely understood, involving a complex interplay between susceptibility genes, metabolic pathways, and environmental factors like diet. The role of oxylipins remains unclear though they may be linked to GDF-15 – a hormone implicated in HG.^4,5 The new method will be valuable in addressing these factors since it provides a link between diet, lipid metabolism, and clinical manifestations of HG. The method will be particularly useful in studies concerning GDF15 given its associations with the lipid metabolism and its involvement, along with its receptor, in the mechanism of nausea and vomiting.

Keywords: Mass spectrometry, LC-MS/MS, oxylipins, HKUST-1, biomarkers, hyperemesis gravidarum

References

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2. Szczuko, M. et al. The Role of Arachidonic and Linoleic Acid Derivatives in Pathological Pregnancies and the Human Reproduction Process. Int J Mol Sci 21, doi:10.3390/ijms21249628 (2020).

3. Wood, E. M., Hornaday, K. K. & Slater, D. M. Prostaglandins in biofluids in pregnancy and labour: A systematic review. PLoS One 16, e0260115, doi:10.1371/journal.pone.0260115 (2021).

4. Fejzo, M. et al. GDF15 linked to maternal risk of nausea and vomiting during pregnancy. Nature 625, 760-767, doi:10.1038/s41586-023-06921-9 (2024).

5. Lindberg, R., Lindqvist, M., Trupp, M., Vinnars, M. T. & Nording, M. L. Polyunsaturated Fatty Acids and Their Metabolites in Hyperemesis Gravidarum. Nutrients 12, doi:10.3390/nu12113384 (2020).