4 INFLUENCE OF A MATERNAL DIABETES MELLITUS TYPE 1 ON LIPID AND CHOLESTERIN METABOLISM IN RABBIT PRE-IMPLANTATION EMBRYOS.

The incidence of overweight and obesity has reached epidemic levels worldwide. Even more alarming is the increasing prevalence of metabolic diseases in younger children and adolescents. The rate of women with diabetes mellitus in child-bearing age is rising, too. According to the developmental origins of health and disease (DOHaD) paradigm, exposure to a hyperglycaemic environment in utero may programme physiology and metabolism permanently, with long-term consequences for offspring health. Experimental evidence indicates that programming of obesity does occur during early embryo development, a period where many women are unaware of pregnancy. To study effects of maternal diabetes mellitus on early embryo development, we induced a type I diabetes through alloxan treatment of female rabbits. In diabetic rabbits, the triglyceride and cholesterin concentrations were altered in serum and the cholesterin concentration in the uterine secretions was elevated. Lipid content of 6-day-old blastocysts was analysed after Oil Red staining and whole mount histochemistry or with Nile Red by fluorescence-activated cell sorting (FACS). Analysis by FACS revealed an approximately 2-fold increase in lipid droplets in blastocysts grown under diabetic conditions. The expression of genes important for lipid metabolism, such as fatty acid transport protein 4 (FATP4), fatty acid-binding protein 4 (FABP4), carnitine palmitoyltransferase 1 (CPT-1), and lipoprotein lipase (LPL), were determined by real-time PCR and showed distinct differences between diabetic and control blastocysts. Immunohistochemical staining of FABP4 was clearly increased in blastocysts grown under diabetic conditions and showed a cell lineage-specific distribution. Two transcription factors, peroxisome proliferator-activated receptor α (PPARα) and PPARγ, with key functions in lipid metabolism and adipogenic differentiation, were increased in blastocysts from diabetic rabbits. We show that maternal diabetes mellitus leads to alteration in lipid metabolism and to triglyceride accumulation in blastocysts. Its long-lasting consequences (e.g. for adipose cell differentiation) need attention and further investigation. [ABSTRACT FROM AUTHOR]