39 research outputs found

    Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

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    BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate <0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P < 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood

    Early and Late Postnatal Myocardial and Vascular Changes in a Protein Restriction Rat Model of Intrauterine Growth Restriction

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    Intrauterine growth restriction (IUGR) is a risk factor for cardiovascular disease in later life. Early structural and functional changes in the cardiovascular system after IUGR may contribute to its pathogenesis. We tested the hypothesis that IUGR leads to primary myocardial and vascular alterations before the onset of hypertension. A rat IUGR model of maternal protein restriction during gestation was used. Dams were fed low protein (LP; casein 8.4%) or isocaloric normal protein diet (NP; casein 17.2%). The offspring was reduced to six males per litter. Immunohistochemical and real-time PCR analyses were performed in myocardial and vascular tissue of neonates and animals at day 70 of life. In the aortas of newborn IUGR rats expression of connective tissue growth factor (CTGF) was induced 3.2-fold. At day 70 of life, the expression of collagen I was increased 5.6-fold in aortas of IUGR rats. In the hearts of neonate IUGR rats, cell proliferation was more prominent compared to controls. At day 70 the expression of osteopontin was induced 7.2-fold. A 3- to 7-fold increase in the expression of the profibrotic cytokines TGF-β and CTGF as well as of microfibrillar matrix molecules was observed. The myocardial expression and deposition of collagens was more prominent in IUGR animals compared to controls at day 70. In the low-protein diet model, IUGR leads to changes in the expression patterns of profibrotic genes and discrete structural abnormalities of vessels and hearts in adolescence, but, with the exception of CTGF, not as early as at the time of birth. Invasive and non-invasive blood pressure measurements confirmed that IUGR rats were normotensive at the time point investigated and that the changes observed occurred independently of an increased blood pressure. Hence, altered matrix composition of the vascular wall and the myocardium may predispose IUGR animals to cardiovascular disease later in life

    CCDC 1855537: Experimental Crystal Structure Determination

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    Related Article: Jaime M. Murphy, Andrea A.E. Gaertner, Tyler Williams, Colin D. McMillen, Brian A. Powell, Julia L. Brumaghim|2019|J.Inorg.Biochem.|195|20|doi:10.1016/j.jinorgbio.2019.03.001,An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

    CCDC 1969548: Experimental Crystal Structure Determination

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    Related Article: Jaime M. Murphy, Andrea A.E. Gaertner, Amanda M. Owen, Samantha Struder, Colin D. McMillen, Modi Wetzler, Julia L. Brumaghim|2020|Inorg.Chim.Acta|507|119568|doi:10.1016/j.ica.2020.11956

    CCDC 1969552: Experimental Crystal Structure Determination

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    Related Article: Jaime M. Murphy, Andrea A.E. Gaertner, Amanda M. Owen, Samantha Struder, Colin D. McMillen, Modi Wetzler, Julia L. Brumaghim|2020|Inorg.Chim.Acta|507|119568|doi:10.1016/j.ica.2020.11956

    CCDC 1969555: Experimental Crystal Structure Determination

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    Related Article: Jaime M. Murphy, Andrea A.E. Gaertner, Amanda M. Owen, Samantha Struder, Colin D. McMillen, Modi Wetzler, Julia L. Brumaghim|2020|Inorg.Chim.Acta|507|119568|doi:10.1016/j.ica.2020.11956

    CCDC 1969556: Experimental Crystal Structure Determination

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    Related Article: Jaime M. Murphy, Andrea A.E. Gaertner, Amanda M. Owen, Samantha Struder, Colin D. McMillen, Modi Wetzler, Julia L. Brumaghim|2020|Inorg.Chim.Acta|507|119568|doi:10.1016/j.ica.2020.11956
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