Grant: Catalyst Grant: Sex as a Variable in Biomedical Research

Pregnancy with diabetes or gestational diabetes (i.e., maternal diabetes) creates elevated blood sugar levels in the womb, resulting in a variety of birth defects, for example, congenital abnormalities of the kidney and urinary tract (CAKUT). CAKUT is a common medical condition in children whose kidneys are not developed properly during pregnancy and responsible for 34-59% of chronic kidney disease (CKD) in childhood and 31% of pediatric kidney failure in United States and Canada. In addition, there are lifelong consequences for the offspring-increased tendency to develop various disorders, such as metabolic syndrome, hypertension (HTN), obesity, cardiovascular disease and CKD in adulthood, and the development of those debilitating diseases varies between men and women in life. The exact reasons for this phenomenon, called perinatal programming, are poorly understood. In this proposed project, we aim to study the sex/gender regulation role of angiotensin II type 2 receptor (AT2R) which is one of key genes known to be important in the development of CAKUT, in our mouse model of maternal diabetes-induced perinatal programming. There is compelling evidence that as a potential therapeutic target for HTN, cardiovascular disease and CKD, AT2R mediates vascular and renal action via sex/gender dependent manner. Thus, better understanding of the sex-dependent mechanisms that underlie maternal diabetes-induced perinatal programming will help develop a novel sex-specific strategy to prevent programmed diseases and comorbid illness in both sexes. The goal of this project is to gain new insights and help researchers and clinicians to develop HTN and CKD prevention and treatment approaches, with a view to reducing diabetic pregnancy-associated healthcare burdens in Canada and thereby improve the quality of life of Canadians.