Project description:This study used SomaScan v 4.1 to profile>7000 proteins in maternal plasma and asses changes with gestational age and maternal characteristics. The study proposed models to estimate the expected protein abundance so that future datasets can be normalized agains these expected value to obtain Multiples of the Mean values.
Project description:Maternal plasma samples collected longitudinally from pregnant women were profiled using SomaLogic aptamer-based assays in women with normal pregnancy and those who delivered preterm. DiagnosisGA is the gestational age at diagnosis with any disease indicated by the Group variable, and it is set to NA for normal pregnancies. In the Group variable, sPTD stands for spontaneous preterm delivery, and PPROM for preterm premature rupture of membranes. Additional longitudinal samples of the controls, including the two samples included herein, are also available and described in PMID: 28738067.
Project description:To characterize the human plasma microtranscriptome profile at first trimester of pregnancy in presence or not of pregnancy complications, we sequenced microRNAs in plasma samples collected from pregnant women between the 4th and the 16th weeks of pregnancy. We then performed differential expression analyses to assess the miRNA profile diffrences according to the presence of pregnancy complications or not (i.e. Gestational diabetes mellitus, Gestational hypertension or preeclampsia vs. normal pregnancies).
Project description:To characterize the human plasma microtranscriptome profile at first trimester of pregnancy in presence or not of pregnancy complications, we sequenced microRNAs in plasma samples collected from pregnant women between the 6th and the 15th weeks of pregnancy as a replication cohort. We then performed differential expression analyses to assess the miRNA profile diffrences according to the presence of pregnancy complications or not (i.e. Gestational diabetes mellitus, Gestational hypertension or preeclampsia vs. normal pregnancies).
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.
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, 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.
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.
Project description:Metabolic variations occur during normal pregnancy to provide the growing fetus with a supply of nutrients required for its development and to ensure the health of the woman during gestation. Mass spectrometry-based metabolomics was employed to study the metabolic phenotype variations in the maternal plasma that are induced by pregnancy in each of its three trimesters. Nontargeted metabolomics analysis showed that pregnancy significantly altered the profile of metabolites in maternal plasma. The levels of six metabolites were found to change significantly throughout pregnancy, with related metabolic pathway variations observed in biopterin metabolism, phospholipid metabolism, amino acid derivatives, and fatty acid oxidation. In particular, there was a pronounced elevation of dihydrobiopterin (BH2), a compound produced in the synthesis of dopa, dopamine, norepinephrine, and epinephrine, in the second trimester, whereas it was markedly decreased in the third trimester. The turnover of BH2 and tryptophan catabolites indicated that the fluctuations of neurotransmitters throughout pregnancy might reveal the metabolic adaption in the maternal body for the growth of the fetus. Furthermore, 11 lipid classes and 41 carnitine species were also determined and this showed variations in the presence of long-chain acylcarnitines and lysophospholipids in later pregnancy, suggesting changes of acylcarnitines and lysophospholipids to meet the energy demands in pregnant women.