Study of the placental transcriptome and its impact on prenatal andpostnatal neurodevelopment: understanding mechanisms and developingearly biomarkers (PERGOLA) (Instituto de Salud Carlos III, 2025-2027)
Summary
Early mental health problems and neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), affect more than 13% of children worldwide, with evidence of a rising prevalence. Early-life environments, including perinatal stages, play a critical role in shaping both early mental health and the risk of NDDs. A key organ underlying the biological mechanisms of this prenatal influence is the placenta, which protects the fetus and supports early brain development. Placental molecular patterns reflect adaptive responses and pathological deregulation, acting as a molecular bridge linking genetic and prenatal environmental factors with later neurodevelopmental and mental health outcomes. Despite this relevance, the study of placental transcriptomics in healthy populations has been largely overlooked, with few investigations using advanced techniques such as RNA sequencing.
Within this context, this project aims to identify placental transcriptional signatures associated with early mental health indicators and neurodevelopmental outcomes, and to develop early biomarkers to detect neonates at risk. As a secondary aim, we will also examine how broad prenatal environmental factors may relate to these placental molecular hallmarks. To achieve this, we will integrate placental RNA-seq profiles with prenatal and postnatal neurodevelopmental data, including neuroimaging (neurosonography at 32 gestational weeks) and neuropsychological and early mental health assessments up to 48 months, in 400 participants from the population-based birth cohort BiSC in Barcelona.
Overall, this study will deepen our understanding of how placental function shapes early brain and mental health trajectories, and will also examine how prenatal environmental factors may modify these molecular profiles. In doing so, it will support the development of early biomarkers to identify and monitor neonates at risk, enabling timely intervention and contributing to advances in perinatal precision medicine.