Pregnancy is a unique physiologic state in adult females that occurs and resolves over a defined time period. The acute metabolic stress it causes on the mother triggers adaptations with maternal pancreatic islets. Failure of normal islet adaptation is a major contributor to gestational diabetes (GDM).In rodents, insulin-producing beta-cells proliferate causing expansion of beta-cell mass. This expansion is defective in rodent models of GDM. Normally, the gestationally-expanded mass regresses in the early postpartum period. We and others have begun to identify gene expression changes that occur during pregnancy and postpartum in this model system, including how defects in specific genes or signaling pathways contribute to GDM. We recently identified a number genes within specific islet cell types whose expression changes in late pregnancy or postpartum. Amongst these were “immediate early genes” (IEGs) including several transcription factors (TFs) that may regulate survival (or cell death) of beta-cells in late pregnancy. In this proposed project, we will test the hypothesis that IEG-TFs identified in our rodent studies regulate beta-cell mass and function in human pregnancy, and may be dysregulated in GDM. To do so, we will perform immunohistochemical staining for specific IEG-TFs. We will co-stain with hormone markers (insulin, glucagon) to confirm cell type of expression, as well as with a marker of apoptosis (TUNEL) to see if IEG-TF expression correlates with apoptosis or survival of beta-cells in pregnancy or GDM.