Congenital Malformations in Offspring of Diabetic Rats: Experimental Study on the Influence of the Diet Composition and Magnesium Intake

Abstract

In spite of improvements in the treatment of diabetes, the risk of congenital malformations in diabetic pregnancy is three to four times higher than in normal pregnancy. This might be due to the metabolic abnormalities of diabetic pregnancy that also affect mineral metabolism. Since diabetes can lower both maternal and fetal blood Mg levels, and Mg deficiency has been shown to be teratogenic in laboratory animals, we decided to investigate which effects Mg deficiency would have in inducing embryopathy in diabetic animals. Female CD rats were divided into six groups. Groups 1 and 2 were fed a standard diet (Mg content 4,200 ppm), groups 3–6 a purified diet (Mg contents 4,200, 500, 250, or 125 ppm). Groups 2–6 had been made diabetic by an intravenous injection of 50 mg/kg streptozocin 1 week before mating. The rats were killed on day 21 of pregnancy, and the live fetuses were examined for external, skeletal, and visceral malformations. The maternal and fetal blood glucose levels were the same in all diabetic groups. The maternal Mg levels in groups 2 and 3 were the same as in controls, but definitely lower in groups 4–6. Embryotoxicity (embryonic deaths, delayed development, congenital malformations) was higher in the groups fed the purified diet than in group 2, but without a clear relation to the dietary Mg levels. We cannot draw any conclusions about the effects of Mg deficiency in diabetic pregnancy from our results, but they show that the quality of the diet is of major importance in the manifestation of embryotoxicity in diabetes.

Development of Rat Embryos Cultured in Serum from Diabetic Rats

“…However, also under these drastic conditions, the effects on the embryos are indicative of developmental delay more than of a clear teratogenic effect. Similar findings have been shown by our previous experience with in vivo and in vitro experiments on diabetes [8,32,34,[46][47][48]. In this respect, a very interesting and deep critical review of the literature (144 references) has recently been published by Kalter [49], in which the author says: 'So far as the experiments are concerned, it is abundantly clear that the induction of diabetes by chemicals is often inefficient, and that, when induced, diabetes is frequently not teratogenic.…”

Interactive effects of alcohol and diabetes during pregnancy on the rat fetus

“…These included: cleft sternum, malformed ribs (bifurcated or fused ribs), vertebral malformations (arch or center), malformed arm joint, missing bone in skull, etc. A wide spectrum of skeletal malformations was also found in other studies with diabetic rats (Baker et al, 1981;Eriksson et al, 1989a;Giavini et al, 1986;Giavini et al, 1990;Urir-Hare et al, 1989), including fused ribs, malformed vertebrae, scoliosis, absence of the tail together with caudal vertebrae (i.e. sacral dysgenesis), a failure of neural tube fusion, and split sternum.…”

“…The malformations observed included: a variety of facial defects, characterized by smaller lower jaw, no lower jaw, no mouth, tongue exposure, otocephaly, and distorted face; missing tail; umbilical hernia/gastroschisis; severe edema; and ectrodactyly. Malformed fetuses from diabetic dams have frequently been reported in rats (Eriksson et al, 1989a;Eriksson, 1984a;Giavini et al, 1986;Giavini et al, 1990;Urir-Hare et al, 1989). The malformations found in those studies included subcutaneous edema, micrognathia, hepatomphalocoele, exencephaly, absence of the tail (Eriksson et al, 1989a;Eriksson, 1984a;Giavini et al, 1986).…”

Effects of Diets with Different Content in Protein and Fiber on Embryotoxicity Induced by Experimental Diabetes in Rats

“…In a previous study [9] we obtained a dra matic increase of embryotoxicity in diabetic rats fed with a purified normoproteic diet (protein 19%, carbohydrates 62.5%, fat 7.5%, fiber 4%, ash 7%): the frequencies of congeni tal malformations and resorptions were 5.2 and 19.6% respectively, with the standard diet and rose to 46.4 and 59.0% with the nor moproteic diet. An evident amelioration was observed when the protein content in the purified diet was increased: the frequency of malformation was restrained to 14.8% and that of postimplantation loss to 16.5% [10].…”

“…The incidence of congenital malforma tions, rather low in diabetic rats on a standard diet [14], increased dramatically when the animals were fed with a purified normo proteic diet [9] and was reduced by feeding the animals a purified hyperproteic diet [ 10], It is not easy to find an explanation for the uncontrollable polyphagia induced by the normoproteic diet, but it is natural to think of a worsening of the diabetes. In this regard an important role could be played by the low fiber content in a normoproteic diet.…”