In this thesis, we aimed to assess the effects of gestational diabetes mellitus (GDM) on maternal, placental and offspring health using a lean, insulin sensitive mouse model for gestational hyperglycemia. Maternal GDM was induced using a high fat and streptozotocin (HFSTZ) treatment, which resulted in mild hyperglycemia which developed during pregnancy and in most cases returned to normoglycemia postpartum (GDM), or more severe hyperglycemia which already presented prior to mating (PDM) (Chapter 2). Both were characterized by glucose intolerance and inadequate insulin responses. Additionally, hyperglycemia in pregnancy was associated with early liver disease markers in pregnancy and lactation. We next investigated the impact of maternal hyperglycemia on placental function (Chapter 3). GDM reduced the size of the placental labyrinth zone in male placentas. Additionally, we reported alterations in placental metabolism and increased placental immune response, again with more pronounced changes in male placentas. We then aimed to further evaluate effects of gestational hyperglycemia and its severity on the development and growth of the offspring (Chapter 4). We observed transient growth restriction and altered hepatic lipid metabolism in young offspring of both sexes. Lastly, we explored the potential of amino acid supplementation to improve fetal growth by conducting a systematic review (Chapter 5). Supplementation of the arginine family was most widely studied and resulted in promising improvements in fetal growth in pregnancies complicated by fetal growth restriction and/or hypertensive disorders. Overall, the studies conducted in the present thesis provide insights into the pathophysiology of lean GDM and its effects on placenta and offspring. The phenotypes described provide new insights and starting points for further studies, both preclinical and clinical.
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2023|