Diabetic environment and genetic predisposition as causes of congenital malformations in NOD mouse embryos.
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)
Department of Anatomy, Shimane Medical University, Izumo, Japan.
H
H
Otani
O
O
Tanaka
R
R
Tatewaki
H
H
Naora
T
T
Yoneyama
D000818:Animals; D003920:Diabetes Mellitus / Q000503:physiopathology*; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D016688:Mice, Inbred NOD; D009436:Neural Tube Defects / Q000196:embryology / Q000209:etiology* / Q000235:genetics; D009765:Obesity / Q000150:complications*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000503:physiopathology*; D013131:Spine / Q000002:abnormalities*