Placental and humoral alterations in gestational diabetes

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dc.contributor.advisor Staiger, Harald (Prof. Dr.)
dc.contributor.author Stirm, Laura
dc.date.accessioned 2018-07-04T06:47:24Z
dc.date.available 2018-07-04T06:47:24Z
dc.date.issued 2018-07-04
dc.identifier.other 507248554 de_DE
dc.identifier.uri http://hdl.handle.net/10900/82968
dc.identifier.uri http://nbn-resolving.de/urn:nbn:de:bsz:21-dspace-829681 de_DE
dc.identifier.uri http://dx.doi.org/10.15496/publikation-24359
dc.description.abstract Project 1 and 2 focus on the influence of maternal gestational diabetes (GDM) on fetal future health. Epidemiological data indicate that offspring of pregnancies accompanied by maternal GDM have elevated risk of developing overweight and type 2 diabetes (T2D) later in life. Recent results propose that fetal insulin resistance (IR) exists already in utero and could be causative for development of overweight and T2D later. Scientific goal of these projects was to investigate placental GDM-associated alterations contributing to fetal programming. Maternal plasma and placental lipid profiles were prepared. These profiles indicate that elevated amounts of saturated non-esterified fatty acids (SFA, i.e. palmitate) of the maternal circulation can be found in placental tissue and contribute to an elevated placental gene expression of PLIN2 and inflammatory genes (TLR2, IL1B, and IL6). Gene expression of these genes in primary trophoblasts isolated from NGT and GDM women resembles expression in whole placental tissue. Furthermore, stimulation of primary trophoblasts with palmitate leads to increased gene expression of PLIN2, inflammatory genes, apelin (APL) and it’s receptor APJ. Additionally, GDM was shown to be associated with an elevated placental macrophage accumulation. This finding may result from elevated SFA-mediated IL8 expression in placenta of GDM women. Finally, we investigated if GDM-associated alterations of placental lipid profiles and gene expression contribute to differences of cord blood lipid and inflammatory cytokine concentrations or differences in cord blood APL concentrations. As no GDM-associated elevated fetal plasma SFA and inflammatory cytokine concentrations or differences of APL concentration were found we propose that other mechanisms could contribute to GDM-associated development of in-utero IR. In conclusion, our results indicate that GDM-associated alterations do not directly influence fetal metabolism. In-utero development of fetal IR may therefore result from other mechanisms. Additionally to direct metabolic influences of GDM on the placenta and the fetal metabolism, we investigated if epigenetic differences in maternal blood are associated with GDM. Therefore, the miRNA expression profile of maternal blood was compared between NGT and GDM women. An elevated expression of miRNA-340 could be found in maternal whole blood cells (WBC). In-vitro results of this project indicate that insulin increases the expression of this miRNA. Furthermore, a positive correlation between maternal plasma insulin and WBC miRNA-340 is observed. Additionally the influence of the differentially expressed miRNA on poteintial target genes was investigated. A negative correlation between miRNA-340 expression and PAIP1 protein expression in lymphocytes was seen. In maternal cell-free plasma, further GDM-associated miRNA expression patterns are present. Future studies should investigate the predictive value of these new GDM-associated indicators. en
dc.language.iso en de_DE
dc.publisher Universität Tübingen de_DE
dc.rights ubt-podno de_DE
dc.rights.uri http://tobias-lib.uni-tuebingen.de/doku/lic_ohne_pod.php?la=de de_DE
dc.rights.uri http://tobias-lib.uni-tuebingen.de/doku/lic_ohne_pod.php?la=en en
dc.subject.classification Diabetes , Schwangerschaft , Plazenta , Epigenetik de_DE
dc.subject.ddc 570 de_DE
dc.subject.other gestational diabetes en
dc.subject.other placenta en
dc.subject.other inflammation en
dc.subject.other epigenetics en
dc.title Placental and humoral alterations in gestational diabetes en
dc.type Dissertation de_DE
dcterms.dateAccepted 2018-05-29
utue.publikation.fachbereich Pharmazie de_DE
utue.publikation.fakultaet 7 Mathematisch-Naturwissenschaftliche Fakultät de_DE

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