Congenital malformations such as neural tube defects and a kinky or waved vertebral column were observed at higher incidence in embryos from nonobese diabetic (NOD) female mice with overt diabetes (NOD-D; 40.3%, P less than 0.005) or without overt diabetes (NOD-N; 8.4%, P less than 0.05) than in control Institute of Cancer Research (ICR) mouse embryos (1%) at day 13 of gestation. In vivo and in vitro preimplantation development of NOD-N, NOD-D, and ICR embryos did not differ in rate of development, size, or morphology. Embryos cultured from one-cell to early blastocyst stage were mutually transferred to uterine horns of pseudopregnant females between NOD-D and ICR mice and examined at day 13 of gestation. There were significant decreases in ratios of implantation and of viable embryos in ICR embryos transferred to NOD-D recipients (52%, P less than 0.001 and 14%, P less than 0.001, respectively) compared with those ratios in ICR embryos transferred to ICR uteri (79.2 and 56.2%) or those in NOD-D embryos transferred to ICR uteri (70.3 and 33.1%). Furthermore, 18 of 45 viable ICR embryos transferred to NOD-D dams had malformations, whereas there were no malformations in 73 viable ICR embryos transferred to ICR recipients, suggesting deleterious effects of maternal diabetic environment to embryos. On the other hand, 8 of 58 viable NOD-D embryos that were cultured in vitro and transferred to ICR uteri had malformations such as neural tube defects.(ABSTRACT TRUNCATED AT 250 WORDS)

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The chromosomes of postimplantation stage embryos of nonobese diabetic (NOD) mice were analyzed to investigate the causal mechanism of congenital anomalies in diabetic pregnancies. Postimplantation stage embryos (day 12 of gestation) in diabetic (NOD-DM) and nondiabetic (NOD-N) NOD mice had either a high or low incidence of chromosomal abnormalities. A large majority of externally normal embryos from NOD-DM and NOD-N mice had low incidences. A high incidence of chromosomal abnormalities was found in externally abnormal embryos of NOD-DM and NOD-N mice, and in a smaller number of externally normal NOD-N and NOD-DM embryos. No control ICR embryo manifested a high incidence of chromosomal abnormalities. In the NOD-DM embryos, the chromosomes appeared to be influenced by long-term maternal diabetic conditions, while high incidences of chromosomal abnormalities in the NOD-N embryos suggested a probable cause by other factor(s) (e.g. a genetic predisposition) or by a very mild diabetic condition because the NOD-N mice were prediabetic.

Associations of nucleolar organizing regions (NORs) in the postimplantation stage embryos of nonobese diabetic (NOD) mice, and diabetic ICR mice induced by streptozotocin (ST), were studied to investigate the possible cause of the numerical anomalies of the chromosomes in their abnormal embryos. The incidence of NOR associations in abnormal embryos from diabetic NOD (NOD-DM) and STZ-diabetic mice was 11.7 and 7.7%, respectively. This incidence was significantly higher than that (1.2%, p < 0.05) of normal embryos from ICR mice which were used as control. From the results analyzed cytogenetically it was suggested that the higher incidence of chromosomal numerical anomalies in the embryos from NOD-DM and STZ-diabetic mice were caused by the chromosomal nondisjunction induced by associations of NORs. Furthermore, it was suggested that NOD-DM embryos have a tendency to increase the associations of NOR in a diabetic condition together with other factors such as autoimmune disease, however a diabetic condition alone induced chromosomal anomalies. Regarding relationships between the incidence of associations of NOR and the types of malformed embryos, it was also clear that all of the abnormal embryos from NOD-DM and STZ-diabetic mice had a high incidence of associations of NOR, and that the incidence was not related to the types of congenital anomalies. Furthermore, in the mal-developed tissue of embryos from STZ-diabetic mice, many chromosomal anomalies were found (26.6%), and the incidence was similar to that of whole embryos (22.6%). Unexpectedly, the incidence of associations of NOR in the maldeveloped tissue was not higher than that of whole embryos. As the results in this study suggest, the numerical anomalies induced by association of NOR seemed to be a causal factor of the disorder of morphogenesis, rather than a resulting phenomenon in abnormal embryos from diabetic mothers.