Relationship between Associations of NOR and Chromosomal Anomalies in the Abnormal Embryos of Nonobese Diabetic and STZ-Diabetic Mouse

Abstract

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.

Maternal diabetes and oocyte quality

“…Finally, by karyotypic analysis, we confirmed the increased aneuploidy rate in ovulated oocytes from diabetic mice. This is in line with previous reports showing a high frequency of chromosomal numerical anomalies in embryos from diabetic mice (Tatewaki et al, 1995; Yamamoto et al, 1971). Furthermore, mitochondrial dysfunction has been proposed as a factor in the increased incidence of aneuploidy in oocytes from older women (Brenner et al, 1998; Keefe et al, 1995).…”

Analysis of polyploid cells in mouse embryonic cells cultured under diabetic conditions

“…1995). The present results from embryonic cell culture are consistent with the in vivo results from NOD‐DM and STZ‐diabetic mice (Tatewaki et al . 1991, 1995).…”

“…Endoreduplication of cells with structural abnormalities (breaks), in particular, could bring critical changes in the nuclear phase and go into apoptosis. As shown in Table 3, polyploid cells were also frequently observed in the tissue from the malformed part such as exencephaly of D12 embryos from STZ‐diabetic mice (Tatewaki et al . 1995).…”

“…Ratios of the living and dead cells were calculated and statistically analyzed ( t ‐test). D12 embryos from normal ICR mothers were also prepared for chromosomal analysis as described (Tatewaki et al . 1991, 1995).…”

“…1991). An association of the nucleolus organizer region (NOR) seemed to be one of the causes of the numerical abnormalities in the embryos from both diabetic NOD and streptozotocin (STZ)‐induced diabetic mothers (Tatewaki et al . 1995).…”