Effects of metabolic factors in the diabetic state on the in vitro development of preimplantation mouse embryos.
The effects of insulin, glucagon, beta-hydroxybutyrate, and acetoacetate on the in vitro development of preimplantation mouse embryos were studied. In controls, 24% of blastocysts failed to develop successfully when grown for 72 h in Eagle's medium supplemented with 10% fetal calf serum. Insulin at concentrations of 1.0 and 2.0 IU/ml of culture medium interfered with development in 62-63% of the blastocysts. Preimplantation embryos showed a threshold pattern in their reaction to glucagon: its addition in concentrations of 0.0015 mM (5 micrograms/ml) did not significantly inhibit blastocyst development, while concentrations of 0.003 mM (10 micrograms/ml) inhibited 70% of blastocysts. The embryotoxic effects of ketone bodies were manifested only in relatively high doses. beta-hydroxybutyrate was embryotoxic at concentrations greater than 5 mg/ml, and its effects were dose dependent: 48 mM (6 mg/ml) inhibited 45% of blastocysts, while 80 mM (10 mg/ml) arrested 87% of embryos from further development. Acetoacetate at concentrations of 0.1 mM (10 micrograms/ml) inhibited the development of 50% of the blastocysts, and its effects were not dose dependent: concentrations of 1 mM (100 micrograms/ml) inhibited development in 63% of the embryos. The combination of the diabetic metabolic factors in relatively low concentrations was highly embryotoxic, especially when accompanied by hyperglycemia.
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000494:pharmacology*; D000818:Animals; D001755:Blastocyst / Q000187:drug effects / Q000502:physiology*; D046508:Culture Techniques; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005934:Glucagon / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006885:Hydroxybutyrates / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007657:Ketone Bodies / Q000494:pharmacology; D051379:Mice; D011247:Pregnancy; D011254:Pregnancy in Diabetics
D000090:Acetoacetates; D006885:Hydroxybutyrates; D007328:Insulin; D007657:Ketone Bodies; C016635:acetoacetic acid; D005934:Glucagon; D005947:Glucose; D020155:3-Hydroxybutyric Acid