Skip to main content

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

Principal investigator

Project type
Znanstveno-istraživački projekti
Research Projects
Croatian Science Foundation
Start date
Dec 1st 2018
End date
May 31st 2023
Total cost
990000 HRK
More information

Serotonin (5HT) is a multifunctional signaling molecule best known as a neurotransmitter of the central nervous system. In addition, 5HT also plays important extra-cerebral roles, both in adulthood and during development. Disturbances in 5HT homeostasis are associated with many mental health conditions and also appear to play an important role in obesity and diabetes. There is growing evidence that DNA methylation modulates the expression of 5HT-regulating genes and may contribute to 5HT dysfunction. DNA methylation is a dynamic process that responds to environmental cues, especially during early development. Our recent findings suggest that DNA methylation of the 5HT transporter gene (SLC6A4) in the placenta is sensitive to maternal metabolic perturbations associated with gestational diabetes mellitus (GDM). Therefore, this project aims to better understand the influence of maternal metabolic status during pregnancy on the 5HT system of the placenta and the newborn. Using placental tissue and primary placental cells obtained from clinically well-defined normoglycemic and GDM pregnancies, we will investigate the relationship of maternal pre-pregnancy body mass index (pBMI) and gestational glycemia with DNA methylation and expression of SLC6A4, 5HT receptor type 2A (HTR2A) and other serotonin-regulating genes in the placenta. Furthermore, through in vitro studies in placental cell models, we will investigate how exposure to glucose affects methylation and expression of SLC6A4 as well as the function of the corresponding gene product. Finally, we will investigate the relationship of pBMI and gestational glycemia with the neonatal 5HT system by measuring DNA methylation of 5HT-regulating genes and 5HT-related biochemical parameters (5HT levels, platelet 5HT uptake) in cord blood samples.

This site uses cookies.. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and can only be disabled by changing your browser preferences.