Human Plasma Proteome During Normal Pregnancy
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ABSTRACT:
PROVIDER: PRJNA851013 | ENA |
REPOSITORIES: ENA
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Project description:Malaria in pregnancy (MiP) is a public health problem in malaria-endemic areas, contributing to detrimental outcomes for both mother and fetus. Primigravida and second-time mothers are most affected by severe anaemia complications and babies with low birth weight compared to multi-gravida women. Infected erythrocytes (IE) reach the placenta, activating the immune response by placental monocyte infiltration and inflammation. However, specific markers of MiP result in poor outcomes, such as low birth weight, and intrauterine growth restriction for babies and maternal anaemia in women infected with Plasmodium falciparum are limited. In this study, we identified the plasma proteome signature of a mouse model infected with Plasmodium berghei ANKA and pregnant women infected with Plasmodium falciparum infection using quantitative mass spec-trometry-based proteomics. A total of 279 and 249 proteins were quantified in murine and human plasma samples, of which 28% and 30% were regulated proteins, respectively. Most of the regulated proteins in both organisms are involved in complement system activation during malaria in pregnancy. CBA anaphylatoxin assay confirmed the complement system activation by the increase in C3a and C4a anaphylatoxins in the infected plasma compared to non-infected plasma. Moreover, correlation analysis showed the association between complement system activation and reduced head circumference in newborns from Pf-infected mothers. The data obtained in this study highlight the correlation between the complement system and immune and newborn outcomes resulting from malaria in pregnancy.
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Project description:Emerging evidence has revealed alterations of microRNA (miRNA) profiles in peripheral blood associated to changes in a range of physiological conditions, suggesting that circulating miRNA profiles could be used as prognostic and/or diagnostic biomarkers for a wide variety of clinical conditions. Normal human pregnancy poses an extensive number of physiological challenges, affecting virtually every level of the pregnant woman’s biology, as well as changing contributions of the placenta and fetus. In this cohort study, using longitudinal large-scale profiling of circulating miRNAs at four defined stages during and after normal pregnancy, relative to non-pregnant controls, we investigate temporal changes in miRNA profiles as potential biomarkers of pregnancy evolution. By comparing the profiling of blood plasma miRNAs with available expression data, we found that miRNAs most prominently expressed in key reproductive tissues are collectively down regulated throughout pregnancy. Furthermore, we find a bias in the proportion of differentially expressed miRNAs associated with fetal sex right from the first trimester. Lastly, by combining circulating miRNAs expression with fetal growth indicators derived from the same women, we identify a robust miRNA signature associated to fetal growth during normal pregnancy. Our results demonstrate the existence of temporal changes of specific miRNAs associated to distinct aspects of pregnancy, including correlates of placental function, fetal gender, and fetal growth, as well as an early lactation related signature; strongly suggesting the potential of peripheral miRNAs as biomarkers of normal pregnancy.
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