Aberrant patterns of cellular communication in diabetes-induced embryopathy. I. Membrane signalling.
OBJECTIVE
Our purpose was to investigate the role of membrane signalling in the mechanism of diabetes-induced embryopathy.


METHODS
Three groups of 70-90-day-old Sprague-Dawley rats were employed in our study: group 1 was normal control rats receiving a normal diet; group 2 represented experimentally induced diabetic rats with malformed offspring (intravenous injection of 65 mg/kg streptozotocin on pregnancy day 6) and group 3 included streptozotocin-induced diabetic rats with normal offspring. Embryos were examined on day 12 under light microscopy, categorized as morphologically normal or defective, and yolk sac cells were harvested from each group. Activities of ERK1 and 2, Raf-1, JNK1 and 2 in yolk sac cells were analyzed by Western blot with primary antibodies specific to the phosphorylated kinases, respectively.


RESULTS
A strong link between hyperglycemia and congenital malformations was confirmed. Key mitogen-activated protein kinases serve as syllabic intermediates: increased activities of Jun-amino-terminal kinase (JNK1 and 2) and decreased activities of extracellular signal-regulated kinase (ERK1 and 2) were observed during hyperglycemia-induced embryopathy.


CONCLUSIONS
Poorly controlled maternal diabetes results in embryopathy which is mediated via a pattern of aberrant cellular communication manifested by both macroscopic and microscopic membrane injury.
Reece
E A
EA
Department of Obstetrics and Gynecology, Chemistry and Molecular Biology, The University of Arkansas College of Medicine, Little Rock 72205, USA.
Ma
X D
XD
Wu
Y K
YK
Dhanasekaran
D
D
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D002450:Cell Communication / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D003921:Diabetes Mellitus, Experimental; D005260:Female; D005315:Fetal Diseases / Q000209:etiology* / Q000503:physiopathology*; D006943:Hyperglycemia / Q000150:complications*; D020935:MAP Kinase Signaling System / Q000502:physiology; D023421:Models, Animal; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000150:complications* / Q000503:physiopathology*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013311:Streptozocin
D015415:Biomarkers; D013311:Streptozocin; D017346:Protein Serine-Threonine Kinases