Health + Life Science Alliance Heidelberg Mannheim

Prenatal maternal stress is associated with an increased risk for adverse physical outcomes as well as behavioral and neurodevelopmental problems in the offspring. The molecular mechanisms mediating the long-term effects of this exposure are not well understood. Given that the placenta plays a central role in neurodevelopment and orchestrates complex maternal-fetal interactions, modifications of the placental epigenome provide a potential link between prenatal stress exposure and changes in gene expression that could initiate fetal programming signatures. This project is based on data from the prospective birth cohort study POSEIDON ("Pre-, peri- and pOstnatal Stress in human and non-human offspring: A translational approach to study Epigenetic Impact on DepressiON"), which comprised 410 healthy mother-infant dyads, recruited during the third trimester of pregnancy from hospitals in the Rhine-Neckar Region. In a first step, I identifed epigenome-wide differentially methylated positions and regions in the placenta that are associated with maternal stress and psychopathology during pregnancy study (Müller et al., in prep). In a next step, I plan an integrated analysis of DNA methylation and gene expression patterns in placental tissue in order to infer the functional significance of the epigenetic signatures and to gain further insights into the interplay between molecular genetic and environmental factors in early programming. In addition to these analyses in bulk tissue, single cell analyses are planned as with these specialized analyses, we are able to study thousands of genes expressed in individual cells. For this project, a subsample of mothers with high prenatal stress (n=8) and age-matched mothers with low prenatal stress (n=8) will be carefully selected.