Effect of diabetes mellitus on mouse pre-implantation embryo development

Fifteen spontaneously diabetic, non-obese mice (NOD strain), 17 nondiabetic NOD mice (in which diabetes had not yet developed) and 9 diabetic NOD mice were treated with insulin. All animals were superovulated with 5 iu of pregnant mares' serum gonadotrophin followed 48 h later by 5 iu human chorionic gonadotrophin (hCG) and mated overnight with NOD males of proven fertility. To assess in-vitro and early in-vivo development, 23 NOD mice were killed 72 h after hCG treatment. Embryos were recovered from oviduct flushings and cultured in Ham's F-10 medium with 0.1% bovine serum albumin at 37°C in an atmosphere of 5% O₂, 5% CO₂ and 90% N₂. Development was assessed at intervals of 24 h for 72 h. Compared with embryos from non-diabetic NOD mice (n = 81), embryos from diabetic NOD mice (n = 68) demonstrated marked impairment in growth assessed by distribution of developmental stages at each observation period (24, 48, 72 h, all P < 0.001) and by overall rates of progression of developmental stages (P < 0.01). In diabetic NOD mice treated with insulin, embryo development (n = 71) was not significantly different from that of embryos from non-diabetic NOD mice (n = 81), but was significantly faster than in embryos from diabetic NOD mice not treated with insulin (n = 68) (P < 0.001, for all periods, overall rate P < 0.01). To assess late in-vivo growth, 18 NOD mice were killed 120 h after hCG. Distribution of developmental stages was significantly retarded among embryos from diabetic NOD mice (n = 115) compared with embryos from nondiabetic NOD mice (n = 117) (P < 0.001 at all times), and with embryos from NOD diabetic mice treated with insulin (n = 29) (P < 0.001). We therefore conclude that uncontrolled spontaneous diabetes mellitus per se retards embryo development of mice in vivo and in vitro.