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Urinary Proteomic Profiling in Pregnancies Affected by Fetal Aneuploidies

ABSTRACT: Mass spectrometry-based proteomics has greatly advanced our understanding of biological processes across diverse fields, including disease and oncology. Despite this progress, the maternal-fetal interface, particularly in the context of fetal aneuploidy, remains underexplored. This study addressed this gap by performing an exploratory, label-free mass spectrometry-based proteomic analysis of maternal urine from 15 pregnancies with normal karyo-type and 9 with fetal aneuploidy.

INSTRUMENT(S): SYNAPT G2-Si

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Iuga Cristina-Adela

PROVIDER: MSV000099309 | MassIVE |

SECONDARY ACCESSION(S): PXD068958

REPOSITORIES: MassIVE

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Project description:Activation of the maternal immune system during pregnancy can fetal development, which can lead to postnatal susceptibility to a wide range of diseases, including cardiovascular, metabolic and psychiatric disorders. During maternal immune activation (MIA), the maternal body must balance its ressources between mounting an immune response and investing resources into continued metabolism and growth : both essential for survival of the fetus and a successful pregnancy. How the placenta responds to MIA over time and how it can protect the fetus is not well understood, and neither are the fetal consequences of MIA. Here, we characterised the response to an induced acute inflammation in maternal lungs over time across maternal and fetal organs, using a combination of omics-methods, imaging and integrative computational analysis. We found that the placenta, unlike other maternal organs, did not react by inducing a typical inflammatory response, but instead initially induced genes associated to strengthen tissue integrity and simultaneously reduced growth to prevent exposure to potential infections. Afterwards, a return to homeostasis was observed, with heightened biosynthesis and expression of endoplasmic reticulum (ER) stress genes. This mechanism likely protects the fetus from inflammation, as we observed no immune response in the fetal liver transcriptome. Instead, we observed metabolic adaptations in the fetus, including a release of docosahexaenoic acid (DHA) Notably, DHA has a crucial function for fetal brain development , and levels of triglyceride and phosphatidylcholine lipids that are necessary for transportation of DHA to the brain were also increased. This metabolic response is likely a combination of the placental MIA response and temporary maternal fasting, caused by MIA-induced fever and lack of nutrient intake. Our study shows, for the first time, the temporal and systemic response to MIA in lungs across maternal and fetal organs.

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Urinary Proteomic Profiling in Pregnancies Affected by Fetal Aneuploidies

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