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Epigenetic consequences of placental dysfunction

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Titel: Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development
Auteur: Baardman, Maria E., Zwier, Mathijs V., Wisse, Lambertus J., Gittenberger-de Groot, Adriana C., Kerstjens-Frederikse, Wilhelmina S., Hofstra, Robert M. W., Jurdzinski, Angelika, Hierck, Beerend P., Jongbloed, Monique R. M., Berger, Rolf M. F., Plösch, Torsten, DeRuiter, Marco C.
Magazine: Disease Models & Mechanisms
Titel: In utero sFlt-1 exposure differentially affects gene expression patterns in fetal liver
Auteur: Stojanovska, V., Holwerda, K. M., van der Graaf, A. M., Verkaik-Schakel, R. N., Boekschoten, M. V., Faas, M. M., Scherjon, S. A., Plösch, T.
Magazine: Journal of Developmental Origin of Health and Disease
Titel: Sex-specific placental differences as a contributor to sex-specific metabolic programming?
Auteur: Pruis, M. G. M., Gellhaus, A., Kühnel, E., Lendvai, Á., Bloks, V. W., Groen, A. K., Plösch, T.
Magazine: Acta Physiologica
Titel: LEVER
Titel: Sex-specific placental differences as a contributor to sex-specific metabolic programming?
Auteur: Pruis MG, Gellhaus A, Kühnel E, Lendvai Á, Bloks VW, Groen AK, Plösch T.
Magazine: Acta Physiologica
Titel: Placental-Specific Overexpression of sFlt-1 Alters Trophoblast Differentiation and Nutrient Transporter Expression in an IUGR Mouse Model
Auteur: Kühnel, Elisabeth, Kleff, Veronika, Stojanovska, Violeta, Kaiser, Stephanie, Waldschütz, Ralph, Herse, Florian, Plösch, Torsten, Winterhager, Elke, Gellhaus, Alexandra
Magazine: Journal of Cellular Biochemistry
Titel: Preeclampsia As Modulator of Offspring Health
Auteur: Stojanovska, Violeta, Scherjon, Sicco A., Plösch, Torsten
Magazine: Biology of Reproduction
Titel: A double-hit pre-eclampsia model results in sex-specific growth restriction patterns
Auteur: Stojanovska, Violeta, Dijkstra, Dorieke J., Vogtmann, Rebekka, Gellhaus, Alexandra, Scherjon, Sicco A., Plösch, Torsten
Magazine: Disease Models & Mechanisms
Titel: Lipotoxicity and the role of maternal nutrition
Auteur: Pruis MG, van Ewijk PA, Schrauwen-Hinderling VB, Plösch T.
Magazine: Acta Physiologica
Titel: Epigenetic programming at the Mogat1 locus may link neonatal overnutrition with long-term hepatic steatosis and insulin resistance
Auteur: Ramon-Krauel, Marta, Pentinat, Thais, Bloks, Vincent W., Cebrià, Judith, Ribo, Silvia, Pérez-Wienese, Ricky, Vilà, Maria, Palacios-Marin, Ivonne, Fernández-Pérez, Antonio, Vallejo, Mario, Téllez, Noélia, Rodríguez, Miguel Àngel, Yanes, Oscar, Lerin, Carles, Díaz, Rubén, Plosch, Torsten, Tietge, Uwe J. F., Jimenez-Chillaron, Josep C.
Magazine: The FASEB Journal
Titel: DNA Methylation and Expression Patterns of Selected Genes in First-Trimester Placental Tissue from Pregnancies with Small-for-Gestational-Age Infants at Birth1
Auteur: Leeuwerke, Mariëtte, Eilander, Michelle S., Pruis, Maurien G.M., Lendvai, Ágnes, Erwich, Jan Jaap H.M., Scherjon, Sicco A., Plösch, Torsten, Eijsink, Jasper J.H.
Magazine: Biology of Reproduction
Titel: Diabetes Mellitus in Pregnancy Leads to Growth Restriction and Epigenetic Modification of the Srebf2 Gene in Rat Fetuses
Auteur: Golic, Michaela, Stojanovska, Violeta, Bendix, Ivo, Wehner, Anika, Herse, Florian, Haase, Nadine, Kräker, Kristin, Fischer, Caroline, Alenina, Natalia, Bader, Michael, Schütte, Till, Schuchardt, Mirjam, van der Giet, Markus, Henrich, Wolfgang, Muller, Dominik N., Felderhoff-Müser, Ursula, Scherjon, Sicco, Plösch, Torsten, Dechend, Ralf
Magazine: Hypertension
Titel: Influence of relative NK-DC abundance on placentation and its relation to epigenetic programming in the offspring
Auteur: Freitag N, Zwier MV, Barrientos G, Tirado-González I, Conrad ML, Rose M, Scherjon SA, Plösch T*, Blois SM*. (*equally contributed)
Magazine: Cell Death and Disease
Titel: Maternal-fetal cholesterol transport in the second half of mouse pregnancy does not involve LDL receptor-related protein 2
Auteur: Zwier, M. V., Baardman, M. E., van Dijk, T. H., Jurdzinski, A., Wisse, L. J., Bloks, V. W., Berger, R. M. F., DeRuiter, M. C., Groen, A. K., Plösch, T.
Magazine: Acta Physiologica
Titel: Early micronutrient supplementation protects against early stress-induced cognitive impairments
Auteur: Naninck, Eva F. G., Oosterink, J. Efraim, Yam, Kit-Yi, Vries, Lennart P., Schierbeek, Henk, Goudoever, Johannes B., Verkaik-Schakel, Rikst-Nynke, Plantinga, Josèe A., Plosch, Torsten, Lucassen, Paul J., Korosi, Aniko
Magazine: The FASEB Journal
Titel: Human sFLT1 Leads to Severe Changes in Placental Differentiation and Vascularization in a Transgenic hsFLT1/rtTA FGR Mouse Model
Auteur: Vogtmann, Rebekka, Kühnel, Elisabeth, Dicke, Nikolai, Verkaik-Schakel, Rikst Nynke, Plösch, Torsten, Schorle, Hubert, Stojanovska, Violeta, Herse, Florian, Köninger, Angela, Kimmig, Rainer, Winterhager, Elke, Gellhaus, Alexandra
Magazine: Frontiers in Endocrinology
Titel: The peroxisome proliferator-activated receptors under epigenetic control in placental metabolism and fetal development
Auteur: Lendvai, Ágnes, Deutsch, Manuel J., Plösch, Torsten, Ensenauer, Regina
Magazine: American Journal of Physiology - Endocrinology and Metabolism
Titel: Placental insufficiency contributes to fatty acid metabolism alterations in aged female mouse offspring
Auteur: Stojanovska, Violeta, Sharma, Neha, Dijkstra, Dorieke J., Scherjon, Sicco A., Jäger, Andrea, Schorle, Hubert, Plösch, Torsten
Magazine: American Journal of Physiology - Regulatory, Integrative and Comparative Physiol
Titel: Fetal programming in pregnancy-associated disorders
Auteur: Stojanovska, Violeta
Link: http://hdl.handle.net/11370/610fdbdd-7917-47b1-b7da-6a8e266b0887

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Samenvatting van de aanvraag

A substantial number of studies in humans and animals show that maternal undernutrition during pregnancy increases the susceptibility to develop chronic disease at adult age (Barker hypothesis; DOHaD hypothesis, Developmental Origins of Health and Disease). In Western countries, however, maternal undernutrition is currently not a relevant health problem. Placental dysfunction, e.g. in preeclampsia, is the leading cause for fetal undernutrition, intrauterine growth restriction (IUGR) and programming of adult (metabolic) disorder in the absence of maternal undernutrition. We here postulate that placental dysfunction leads to long-term adaptations in the epigenome of the intestine, the liver, and possible also in the hypothalamic-pituitary-adrenal axis. Preeclampsia, a severe complication of pregnancy affecting 5-10% of all pregnancies in Western Europe, is a relevant health problem in the Western world. Although preeclampsia is defined by maternal symptoms (hypertension and proteinuria) developing in the second half of pregnancy, it is a leading cause of perinatal mortality and preterm birth. The etiology of preeclampsia is still not completely clear, however, insufficient trophoblast invasion and inflammatory processes are thought to be key factors involved in the development of preeclampsia. Insufficient trophoblast invasion may lead to impaired function of the placenta and may have deleterious effects for the fetus. It causes a reduced transport of nutrients to the fetus, which very often leads to intrauterine growth restriction. Hence, fetuses from preeclamptic mothers are often born small for gestational age. Thus placental dysfunction in preeclampsia will lead to fetal undernutrition. An overwhelming body of evidence links early nutrition, including fetal and neonatal undernutrition, to the development of chronic diseases at adult age. Both in epidemiological studies and in animal experiments, the nutritional supply of the developing embryo, fetus and neonate has been shown to influence the risk to develop chronic diseases like cardiovascular disease and the metabolic syndrome, which are both major health burdens in Western societies. This phenomenon that the early nutritional environment influences physiology at later life is commonly referred to as “metabolic programming”. Several explanations for the long-term consequences of early nutrition have been proposed. Recently, epigenetic mechanisms have been proposed to be involved in metabolic programming: Several key regulators of metabolism can be epigenetically modified in animal models of fetal undernutrition or overnutrition. We here postulate that preeclampsia leads to long-term adaptations in the epigenome of the intestine, the liver, and in the hypothalamic-pituitary-adrenal axis, comparable to the effects observed in children born to undernourished mothers. These epigenetic changes (“programming”) will affect the nutrient uptake by the intestine; handling of metabolites, namely lipids and glucose, in the liver; and ultimately the regulation of satiety via programming of the brain. Taken together, we hypothesize that epigenetic changes play a central role in the long-term health outcome for the affected child after preeclampsia.

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Projectnummer:
91211053
Looptijd: 100%
Looptijd: 100 %
2013
2020
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
Dr. T. Plösch
Verantwoordelijke organisatie:
Universitair Medisch Centrum Groningen