Prevention by maternal pancreatic islet transplantation of hypothalamic malformation in offspring of diabetic mother rats is already detectable at weaning.

Exposure to gestational diabetes (GD) in rats leads to dysplasia of the ventromedial hypothalamic nucleus (VMN), decisively involved into the regulation of body weight and metabolism. Recently, we have shown here that VMN malformation is absent in adult offspring of GD mothers treated by pancreatic islet transplantation during gestation. We therefore now investigated whether VMN malformation and its prevention are already present at the early postnatal end of the critical hypothalamic differentiation period. Already at weaning, the total number of VMN neurons, the volume of the VMN relative to total brain volume, and the numerical density of neurons in the anterior subnucleus of the VMN were reduced in offspring of sham-transplanted mothers (all P<0.05), but did not differ between offspring of islet-transplanted mothers and controls. No morphometric alterations occurred in the paraventricular hypothalamic nucleus. In conclusion, prevention of VMN malformation in offspring of islet-transplanted diabetic mothers is a direct consequence of normalized maternal metabolism during critical perinatal development.