Diabetes-induced embryo malformations and growth retardation are correlated with a variety of biochemical changes including oxidative stress. In this study, we show that the morphological alterations are correlated with progressive and selective changes of
mRNA expression in specific
neurotrophic factors. At embryological stage E-17, diabetes affected both embryo growth and
NGF mRNA expression, which was reduced by as much as 90 and 56% in target tissues of sensory system such as tongue and intestine, respectively. The reduction in retina and heart was around 50%. Conversely, the
mRNA expression of low-affinity
neurotrophin receptor p75 was increased. At birth,
BDNF mRNA expression was affected with a significant generalized reduction,while in vibrissae we observed a reduction of
BDNF and p75 mRNAs and an increase of
NGF. At postnatal day 14, pups from diabetic mothers showed reduced muscle levels of
IGF-I, while we observed a partial impairment of
substance P axonal transport at postnatal day 28. Treatment of diabetic mothers with
silybin, a flavonoid with
antioxidant properties, prevented most of the changes in
neurotrophic factor expression and
substance P axonal transport with no effects on
hyperglycemia and embryo growth retardation. These results indicate that oxidative stress may influence
neurotrophic factor synthesis in target territories during development. In addition, these data suggest that
nervous system abnormalities observed in diabetic
embryopathy may also derive by insufficient
neurotrophic factor biosynthesis involving sequentially
NGF in the embryo and
BDNF and
IGF-I in the early postnatal days.
Insulin treatment of diabetic mothers normalized
hyperglycemia and body growth, with consequent regular embryonic and postnatal development.