Maternal Diabetes and Retarded Preimplantation Development of Mice

Abstract

The streptozocin-induced diabetic (STZ-D) mouse was found to be a suitable model for studying the effects of maternal diabetes on the preimplantation embryo. This study looked at the effects of maternal diabetes on embryonic growth. Female Quakenbush mice were made diabetic (plasma glucose levels >20 mM) by injection of 190 mg/kg i.p. STZ and were superovulated by standard methods. The blastocysts collected on day 4 from diabetic mothers had 8.5% fewer cells and a 35% lower protein synthetic rate than control embryos. Their cellular protein synthetic rate was 19% less than that in controls. Morulae from diabetic mothers also displayed a reduced protein synthetic rate, but this reduction was not seen in the two-cell embryo. Furthermore, blastocysts cultured in vitro from two-cell embryos from diabetic and control mothers displayed similar protein synthetic rates. This infers that the two-cell embryos from diabetic mothers are normal, and the retardation seen in later development in vivo occurs after the two-cell stage while the embryo is still free in the oviductal and uterine environment. Treatment of the diabetic mice with ultralente insulin every 12 h raised the protein synthetic rate of those blastocysts toward control levels, whereas treatment with lente insulin every 8 h recovered the embryo to the same rate as the control embryos. Because insulin has been shown to be mitogenic and stimulates protein synthesis of morulae and blastocysts in vitro, the absence of insulin in the diabetic mothers may be the cause of the retardation observed in their preimplantation embryos.