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Influence of maternal metabolic state on placental and neonatal serotonin system: from DNA methylation to protein function

Principal investigator

Projekti Hrvatske zaklade za znanost

Serotonin (5HT) is a multifunctional signaling molecule, best known as the central nervous system neurotransmitter. In addition, 5HT plays important extra-cerebral roles, both in adulthood and during development. Disturbed 5HT homeostasis has been linked to many mental health conditions and is emerging as important contributor also to obesity and related metabolic disorders. However, causes of 5HT disturbances are yet poorly understood. Rising evidence suggests that DNA methylation, a dynamic process sensitive to environmental cues, plays a crucial role in the regulation of 5HT signaling through modifying transcriptional activity of genes encoding 5HT-regulating proteins (transporters, receptors and enzymes). In order to search for early developmental origins of altered 5HT functioning in humans, here we aim to establish a comprehensive biobank of human perinatal specimens and investigate the impact of altered maternal metabolic state in pregnancy on placental and the newborn's 5HT system. We hypothesize that maternal metabolic, proinflammatory and/or endocrine changes associated with obesity and gestational diabetes mellitus (GDM) may affect placental and fetal 5HT system through DNA methylation-mediated mechanisms. Hence, we aim to: 1) explore the relationship of maternal gestational glycemia and pregestational body mass index (pBMI) with placental DNA methylation and expression of 5HT-related genes known to be functional in human placental cells; 2) explore the relationship of maternal gestational glycemia and pBMI with the newborn's 5HT system by quantifying cord blood DNA methylation of multiple 5HT-regulating genes and measuring cord blood 5HT-related biochemical/functional parameters (5HT level, platelet 5HT uptake and platelet aggregation); 3) investigate in vitro effects of glucose and inflammatory cytokines on DNA methylation and expression of 5HT-related genes as well as on function of the corresponding gene products in human placental cells (trophoblasts and fetoplacental endothelial cells). The obtained results will increase our knowledge about molecular mechanisms that regulate 5HT system during early human development and may lead to better understanding of conditions associated with disturbed 5HT homeostasis.

Other associates

Lipa Čičin-Šain, Institute Ruđer Bošković

Marina Horvatiček, Institute Ruđer Bošković

Maja Kesić, Institute Ruđer Bošković

Petra Baković, Institute Ruđer Bošković

Marina Ivanišević, Clinical Hospital Centre Zagreb

Mirta Starčević, Clinical Hospital Centre Zagreb

Josip Juras, Clinical Hospital Centre Zagreb

Saša Kralik, Clinical Hospital Centre Zagreb

Dubravka Hranilović, University of Zagreb, Faclty of Science

Barbara Nikolić, University of Zagreb, Faclty of Science

Sandra Nakić Radoš, Catholic University of Croatia, Department of Psychology

Maja Anđelinović, Catholic University of Croatia, Department of Psychology

Gernot Desoye, Medical University of Graz

Ute Panzenboeck, Medical University of Graz

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