Timely onset of delivery is a key factor in perinatal outcomes and child health. Preterm birth—birth before 37 weeks of gestation—is the leading cause of mortality in children under 5 years of age worldwide. Survivors are at high risk of neonatal complications and childhood sequelae, including neurodevelopmental disabilities and learning disorders, especially the most premature. Low- and middle-income countries account for the majority of the world's preterm births. Although many socio-demographic, nutritional, medical, obstetric, and environmental factors have been shown to increase the risk of spontaneous preterm birth, its aetiology is imperfectly understood. The duration of gestation or the risk of preterm birth are also complex traits under genetic control from both maternal and fetal genomes. To date, the molecular mechanisms that trigger labor in humans remain elusive. We and others have reconsidered the importance of the complex interactions between immune and stromal cells at the maternal-fetal interface during pregnancy and labor. It is vital to gather comprehensive information about their molecular composition and spatial context. State-of-the-art single cell methods (genomics, spatial proteomics, epigenomics) will be applied to maternal-fetal interface tissues to determine changes during labor. The current project will include i) mouse genetic studies that may identify novel genes involved in the onset of labor, and ii) human studies, taking into account ethnic differences and low- and middle-income countries context. The work proposed here will provide a detailed picture of the maternal interface—how many different subtypes there are as well as their function and interaction—which may be key to understand the onset of labor and preterm birth. This will be necessary for the identification of biomarkers and pharmacological targets for a better prediction and prevention of preterm birth.