Embryopathy in Genetically Diabetic Mice, Yellow KK, and Its Prevention by Maternal Therapy

Abstract

Embryopathy in yellow KK mice with non‐insulin dependent diabetes mellitus was examined among the conceptuses of females mated at 7, 11, and 13 weeks of age. The numbers of corpora lutea and implants were comparable in all maternal age groups. Early embryonic deaths were frequently observed in all maternal age groups (37.7 46.4%), but no significant difference was found among the groups. The incidence of late embryonic deaths was significantly higher in 11‐ and 13‐wk‐old dams (25.6% and 28.8%) than in 7‐wk‐old dams (14.4%). Moreover, in 13‐wk‐old dams, but not in 7‐wk‐old dams, a positive correlation existed between maternal plasma glucose levels on day 18 of pregnancy and late embryonic deaths. Fetuses from 13‐wk‐old dams weighed less than those from 7‐wk‐old dams (0.73 g vs 0.86 g). Yellow KK mice mated at 13 weeks of age were treated with an oral‐hypoglycemic agent, 5‐[4‐(l‐methylcyclohexylmethoxy)benzyl] thiazolidine‐2,4‐dione (ciglitazone), as an 0.1% dietary admixture. Plasma glucose on day 18 of pregnancy was lower in all treated groups (159‐170 mg/dl) than in the untreated control (345 mg/dl). A significant decrease of late embryonic deaths (12.7‐15.6%) and a slight increase of fetal weights (0.79‐0.81 g) were noted when compared with the untreated controls (36.8% and 0.74 g).

Delayed Maturation of Fetal Lung in Yellow KK Mice

“…Although there were no significant differences between the groups in the rate of early death, the rate of late death in the 13-wk-old dams was significantly higher than that in the 7-wk-old dams ( Table 2 ) . These data are similar to those in our previous report (Ooshima and Ihara, 1986). External malformations were found in only one fetus in each group, and they seemed to occur spontaneously.…”

“…These mice spontaneously develop hyperglycemia and hyperinsulinemia with advancing age (Iwatsuka et al, 1970). In this strain of mice, the plasma glucose concentration is about 260 mg/dl at 7 weeks of age and thereafter increases to 500 mg/dl or more by 13 weeks of age (Ooshima and Ihara, 1986). Fetuses from hyperglycemic dams of this strain show a high mortality rate and growth retardation similar to those from insulin dependent diabetic animals, but malformations do not increase (Ooshima and Ihara, 1986).…”

Growth Retardation during Organogenesis in Genetically Diabetic Mice, Yellow KK

“…Yellow KK mice develop genetic non-insulin dependent diabetes mellitus (NIDDM) with advancing age. We previously reported that fetal mortality increases in relation to maternal hyperglycemia in this strain (Ooshima and Ihara, 1986). Moreover, fetal growth has been found to be retarded at term in hyperglycem-ic dams.…”

“…On the other hand, many studies in mice and rats have shown that the fetuses from diabetic dams are smaller than those for their gestational age. In our previous study (Ooshima and Ihara, 1986), we reported that yellow KK mice with maternal hyperglycemia gave birth to term fetuses showing growth retardation and had an increased incidence of late embryonic death accompanying their elevating plasma glucose levels. The late death was considered to be associated with the growth retardation during organogenesis.…”

“…The yellow KK mouse spontaneously develops hyperglycemia and hyperinsulinemia (Iwatsuka et al, 1970). This mouse is nearly normoglycemic up to 6-7 weeks of age, but thereafter the plasma glucose level rises rapidly with advancing age and reaches a peak as high as 500 mg/dl at 13 weeks of age (Ooshima and Ihara, 1986). Also, in dams mated at 7 weeks of age (group A) in this study, the maternal plasma glucose level was almost normal, or just slightly higher, throughout pregnancy (cf.…”