Maternal diabetes in vivo and high glucose concentration in vitro increases apoptosis in rat embryos.
Apoptosis may be involved in diabetes-induced embryonic dysmorphogenesis. We estimated the occurrence of apoptosis in embryos of a rat model for diabetic pregnancy. We found decreased Bcl-2, increased Bax and cleaved Caspase 3 proteins in embryos from diabetic rats. Moreover, we found increased activation of Caspase 3 in cells from embryos previously exposed to a diabetes-like environment (in vivo, in vitro) compared to cells from control embryos, which was normalized by supplementation of N-acetylcysteine or apoptosis inhibitor. We detected increased propidium iodide uptake in embryonic cells exposed to maternal diabetes, a finding confirmed by vital staining. Additionally, we found increased dysmorphogenesis in embryos exposed to a diabetic environment in vivo and in vitro. Exposure to a diabetic milieu during organogenesis increases apoptosis in embryonic cells and dysmorphogenesis in embryos. Enhanced apoptotic rate may have a role in diabetic embryopathy by inducing disturbed embryonic maturation, increased rates of resorptions and congenital malformations.
Gäreskog
Mattias
M
Department of Medical Cell Biology, Uppsala University, Biomedical Center, PO Box 571, SE-751 23 Uppsala, Sweden. Mattias.Gareskog@medcellbiol.uu.se
Cederberg
Jonas
J
Eriksson
Ulf J
UJ
Wentzel
Parri
P
D000014:Abnormalities, Drug-Induced; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000187:drug effects / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects* / Q000502:physiology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005947:Glucose / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D009924:Organ Culture Techniques; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D005947:Glucose