Manifestations of diabeters mellitus on mouse preimplantation developement: Effect of elevated concentration of metabolic intemediated

The metabolic derangements of pregnancies complicated by diabetes mellitus, specifically hyperglycaemia and hyper-ketonaemia, are known to be teratogenic during the period of organogenesis in animals. We have shown previously that poorly controled diabetes mellitus impairs in-vivo and in-vitro mouse preimplantation embryo growth, and that culturing embryos in elevated glucose concentrations only partially recreated this developmental dealy. To extend this observation we examined the effect on mouse preimplantation embryo growth of elevated concentrations of other metabolic intermediates, which may be deranged in diabetes mellitys, namely lipids, lactate, glycerol, amino acids, and ketones. Two-cell embryos from ovulation-induced B₆C₃F₁ mice were cultured for 72 h in the presence of added lipids (250 mg/dl), lactate (5 mM), glycerol (160 μM) or mixed amino acids (8.5% travosol, 7 mM) and showed no significant difference in growth over 72 h verus their control groups. However, growth of preimplantation embryos in acetoacetate (10 mM) or in the racemic micture of DL-β-hydroxybutyrate (16 and 32mM) revealed marked retardation versus controls when assessed either by distribution of developmental stages over time (24, 48, 72 h, P <0.001) or by the difference in the average rank of sums indicating a delay in maturation (P<0.0001). We conclude that elevated ketone concentrations adversely affect preimplantation embryo development. These findings extend previous studies which correlate uncontrolled diabetes mellitus as well as hyperglycaemia with abnormal organogenesis, and demonstrate tht exposure to metabolic derangements may also hinder reproductive performane at even earlier stages in gestation.