Genotoxicity and diabetic embryopathy: impaired expression of developmental control genes as a cause of defective morphogenesis.
Since the advent of insulin therapy for diabetes mellitus, the survival of mothers with diabetes prior to pregnancy and their offspring has greatly improved. Nevertheless, the observation that the earliest stages of organogenesis can be impaired in the offspring of women with diabetes raises the question of how abnormal fuel metabolism disturbs embryogenesis. Research into this process has been made possible in recent years by advances in molecular biology which makes it possible to study gene expression in early embryos, and by the availability of genetically engineered mutant mouse strains. Using these approaches, a model is emerging in which elevated glucose, by disturbing expression of genes which regulate embryonic development and cell cycle progression, causes premature cell death of emerging organ structures, thereby causing defective morphogenesis. Investigation into the signaling mechanisms by which excess glucose metabolism exhibits toxic effects on embryo gene expression will explain how diabetic embryopathy occurs on a molecular and cellular level, as well as increase our understanding of the role of metabolic homeostasis in proper embryonic development.
Chang
T I
TI
Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.
Loeken
M R
MR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle; D000013:Congenital Abnormalities / Q000209:etiology / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006706:Homeostasis; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D051379:Mice; D009436:Neural Tube Defects / Q000209:etiology / Q000235:genetics; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000150:complications*
D005947:Glucose