Potential role of somatomedin inhibitors in the production of diabetic embryopathies.
Mouse conceptuses at the 18-21-somite stage were grown for 2-24 h in vitro in the presence of a serum fraction (Mr = 800-1,080 daltons) possessing somatomedin-inhibitory activity (SI) isolated from diabetic rats. Following an 8-h exposure to the SI, DNA and incorporation of 3H-thymidine were reduced in the embryos while 12 h was required to observe a reduction in total protein and RNA. At the 24-h time point, the neurectoderm was thinner than in controls, and autoradiograms of this region showed a substantial decrease in grain density with 3H-thymidine, but not 3H-leucine or -uridine. Effects of the visceral yolk sac (VYS) preceded those on the embryo. The cytoplasm of the VYS endoderm cells from conceptuses exposed to the SI contained many vacuoles by 4 h, which were larger by 24 h. Total protein was greater than in controls from 4 h onward, although 3H-leucine incorporation, which had increased after 2 h of SI exposure, returned to control levels by 8 h. As seen by SDS-polyacrylamide gel electrophoresis, VYSs from conceptuses exposed to the SI for 4 or 24 h were enriched (compared to control VYSs) in four protein bands also present in the culture medium (primarily rat serum), suggesting that protein degradation and/or transfer of amino acids and peptides to the embryo was inhibited in these VYSs. Such a conclusion was supported by a quantitative decrease in proteins and amino acids in the exocoelomic fluid of conceptuses exposed to the SI for 24 h. The altered processing of proteins may therefore represent a primary cause of the SI-induced embryonic abnormalities.
Balkan
W
W
Department of Cell Biology and Anatomy, School of Medicine, University of North Carolina, Chapel Hill 27599-7090.
Phillips
L S
LS
Goldstein
S
S
Sadler
T W
TW
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000032:analysis / Q000378:metabolism; D005260:Female; D005315:Fetal Diseases / Q000139:chemically induced* / Q000209:etiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011254:Pregnancy in Diabetics; D051381:Rats; D013002:Somatomedins / Q000037:antagonists & inhibitors* / Q000502:physiology
D013002:Somatomedins