Gamma-linoleic acid and ascorbate improves skeletal ossification in offspring of diabetic rats

Abstract

Maternal diabetes causes a range of complications in offspring, including reduced skeletal ossification. This study examined whether feeding γ-linoleic acid (GLA) and ascorbate, alone or in combination, to diabetic pregnant rats improves skeletal development in their offspring. In addition, Ca2+ concentration was monitored in maternal plasma and fetal tissue, as well as placental mRNA expression of calbindin-D9k. Female rats rendered diabetic with streptozotocin were fed GLA (500 mg/kg/d), ascorbate (290 mg/kg/d), ascorbyl-GLA (790 mg/kg/d), or GLA and ascorbate (500 and 290 mg/kg/d, respectively) throughout pregnancy. Fetal skeletons were studied after alizarin red staining. Fewer ossification centers were observed in offspring of diabetic rats compared with offspring of control rats (68 ± 4% of control, p = 0.01). An almost complete restoration of ossification occurred with all the treatments (92-95 ± 3% of control). The effects of treatment on fetal ossification could not be explained by altered maternal plasma Ca2+ concentrations or by mRNA expression of the placental Ca2+-transporting protein calbindin-D9K. We conclude that GLA and/or ascorbate treatment was effective against diabetes-induced fetal ossification defects by a mechanism not related to placental Ca2+ supply.