Hyperglycemia-Induced Embryonic Dysmorphogenesis Correlates With Genomic DNA Mutation Frequency In Vitro and In Vivo

摘要

Congenital malformations affecting multiple organ sys- tems are at least three times more common in infants of mothers with IDDM than in infants born to nondiabetic mothers. Numerous studies have confirmed the terato- genic effect of hyperglycemia on the developing embryo, although no direct mechanism has been determined. In this study, we aimed to correlate the frequency of lacI mutations with degree of hyperglycemic exposure and severity of malformations in mouse embryos from in vitro cultures. Day 8 transgenic mouse embryos cul- tured in 30 or 50 mmol/1 glucose for 48 h exhibited a higher incidence of morphological abnormalities, as well as an increase in lacI mutation frequency, com- pared with embryos cultured in 10 mmol/l glucose with no abnormalities and a lower frequency of lacI muta- tions.