Early-life exposure is a critical factor in determining disease risk later in life, but we still lack a clear understanding of how disease condition in pregnancy shapes long-term health outcomes. Our previous research used disease-relevant mouse model to mimic type 1 diabetes (T1D) and revealed that dysfunctional placentas due to mild glucose level lead to sex-specific health issues in sons and daughters. We therefore want to understand how the placenta as a key player, programe the development of vital organs to cause the future physiological dysfunction. Using advanced tools like metabolomics, spatial proteomics, and organoids-on-a-chip, we investigate how mitochondrial dysfunction in the placenta affects hormone production and organ function. Combined with our unique patient cohort of T1D and access to recruit children to mother with T1D, our translational study aims to uncover new treatments with targeted nanoparticle treatment to eventually improve life-long health outcomes.