Aberrant patterns of cellular communication in diabetes-induced embryopathy in rats: II, apoptotic pathways.
OBJECTIVE
The objective was to test the hypothesis that hyperglycemia-induced injury of yolk sac cell membranes is associated with disruption of cellular apoptotic signaling pathways.


METHODS
Pregnant rats were induced to become diabetic by injection of streptozotocin. Fourteen normal control and 24 diabetic rats were killed on day 12 of gestation. Yolk sac membranes in 3 conceptus groups (nondiabetic, diabetic with normal, or diabetic with malformed conceptus) were collected for study. DNA was extracted from yolk sac cells and assayed for fragmentation by using gel electrophoresis, which indicates apoptosis. Protein expression was evaluated by Western blot assays. Statistical analyses were performed with the Student t -test.


RESULTS
The level of phosphorylated Akt was significantly decreased, whereas that of the proapoptotic protein Bax was increased. These changes were correlated with the presence of DNA fragmentation in yolk sac cells of the diabetic malformed conceptuses.


CONCLUSIONS
Hyperglycemia-induced embryopathy involves apoptosis, during which the expression of proapoptotic protein Bax is upregulated and the activity of the cell-survival factor, Akt kinase, is decreased in yolk sac cells. These observations suggest that hyperglycemia of maternal diabetes triggers apoptotic signaling pathways and inhibits cell survival pathways, leading to embryonic malformations.
Reece
E Albert
EA
Department of Obstetrics and Gynecology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA. reeceealbert@uams.edu
Ma
Xiang-Dong
XD
Zhao
Zhiyong
Z
Wu
Ying-King
YK
Dhanasekaran
Danny
D
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002450:Cell Communication / Q000502:physiology*; D053938:DNA Fragmentation; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D004622:Embryo, Mammalian / Q000473:pathology*; D005260:Female; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000473:pathology* / Q000503:physiopathology*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt