Poster Presentation Australasian Diabetes in Pregnancy Annual Scientific Meeting 2012

Altered Kidney Development in Offspring of Diabetic and Insulin-Treated Pregnancy  (#64)

Stacey Hokke 1 , James Armitage 1 , Victor Puelles 1 , Kieran Short 2 , Lynelle Jones 2 , Ian Smyth 2 , John Bertram 1 , Luise Cullen-McEwen 1
  1. Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia
  2. Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia

Hyperglycemia is recognised to alter fetal kidney development in animal models. However, the precise effects of diabetic pregnancy on the key processes of kidney development are unclear due to the paucity of studies and limitations in previous methodologies. The purpose of the present study was to better elucidate the effects of hyperglycemia on ureteric branching morphogenesis and nephrogenesis. Type 1 diabetes was induced in pregnant C57Bl/6J mice using multiple dose streptozotocin (STZ) from embryonic day (E) 6.5-8.5. Branching morphogenesis was quantified for the first time ex vivo using Optical Projection Tomography, and nephrons were counted using unbiased stereology. Hyperglycemia was recognised from E12.5 and was associated with a marked reduction in ureteric tip number (control 283.7±23.3 vs. STZ 153.2±24.6, mean±SEM, p<0.01) and ureteric tree length (control 33.1±2.6 mm vs. STZ17.6±2.7 mm, p=0.001) at E14.5, reduced nephron endowment at E18.5 (control 1246.2±64.9 vs. STZ 822.4±74.0, p<0.001), and fetal growth restriction at E14.5 and E18.5. Duplex ureter was a common observation in embryos of diabetic pregnancy. Lowering maternal glucose levels to baseline in late gestation by insulin treatment did not normalise fetal weight or prevent the nephron deficit. The detrimental effect of hyperglycemia on ureteric branching morphogenesis and, in turn, nephron endowment in the growth-restricted fetus highlights the importance of glycemic control in early gestation during the initial stages of renal development.