Decreased Cardiac Glutathione Peroxidase Levels and Enhanced Mandibular Apoptosis in Malformed Embryos of Diabetic Rats

OBJECTIVE— To characterize normal and malformed embryos within the same litters from control and diabetic rats for expression of genes related to metabolism of reactive oxygen species (ROS) or glucose as well as developmental genes

The status of diabetic embryopathy

Diabetic embryopathy is a theoretical enigma and a clinical challenge. Both type 1 and type 2 diabetic pregnancy carry a significant risk for fetal maldevelopment, and the precise reasons for the diabetes induced teratogenicity are not clearly identified. The experimental work in this field has revealed a partial, however complex, answer to the teratological question, and we will review some of the latest suggestions

High-fat diet in pregnant rats and adverse fetal outcome

Background: Although pregestational obesity has been associated with increased risk of adverse fetal outcome, the mechanisms behind are not known. We aimed to investigate the influence of the maternal metabolic state on fetal outcome in rats exposed to either a high-fat diet (HFD) or a control diet (CD). We also investigated the impact of serum collected from HFD/CD pregnant rats on CD embryonic development in whole-embryo cultures. Material and methods: On gestational day 0, 9, 10, or 20 maternal plasma/serum samples were collected as pregnancies were terminated for the estimations of maternal metabolic state and embryo-fetal development. We measured embryonic gene expression of ROS scavenger enzymes as well as genes involved in inflammation in maternal adipose tissue. Results: In HFD maternal plasma/serum, concentrations of glucose, β-hydroxybutyrate, branched-chain amino acids, and leptin were increased, whereas those of triacylglycerol, cholesterol, and palmitic, oleic, linoleic, and α-linolenic acids were decreased. Gene expression of CuZnSOD, IL-6, IL-10, and resistin was increased in HFD maternal adipose tissue, whereas that of CuZnSOD and MnSOD was decreased in HFD-exposed embryos. HFD caused retention of most fatty acids in the maternal liver as well. Conclusion: HFD alters the maternal metabolic state, increases fetal resorptions in vivo, and increases the rate of fetal/embryonic malformations both in vivo and in vitro. These findings suggest that metabolic disturbances in HFD pregnant rats have profound adverse developmental effects in the offspring