Potential role of somatomedin inhibitors in the production of diabetic embryopathies
- 1 March 1988
- journal article
- research article
- Published by Wiley in Teratology
- Vol. 37 (3), 271-282
- https://doi.org/10.1002/tera.1420370313
Abstract
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 on 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.This publication has 33 references indexed in Scilit:
- The Effects of High-Sucrose Diets and of Maternal Diabetes on the Ultrastructure of the Visceral Yolk Sac Endoderm in Rat Embryos Developing in vivo and in vitroCells Tissues Organs, 1987
- In vitro studies on the effect of yolk sac antisera on functions of the visceral yolk sac: I. Pinocytosis and transport of small moleculesTeratology, 1986
- Somatomedin inhibitors from diabetic rat serum alter growth and development of mouse embryos in cultureDiabetes, 1986
- Uptake and distribution of exogenous serum proteins in the cultured rat embryoJournal of Experimental Zoology, 1984
- Nutrition and somatomedin. XI. Studies of somatomedin inhibitors in rats with streptozotocin-induced diabetesDiabetes, 1983
- Malformations in infants of diabetic mothersTeratology, 1982
- WHOLE‐EMBRYO CULTURE AND THE STUDY OF MAMMALIAN EMBRYOS DURING ORGANOGENESISBiological Reviews, 1978
- 5-FU in chick embryos as a source of label for DNA and a depressant of protein synthesisTeratology, 1974
- Lysosomal Enzyme Inhibition by Trypan Blue: A Theory of TeratogenesisScience, 1967
- CONGENITAL MALFORMATIONS IN NEWBORN INFANTS OF DIABETIC WOMEN CORRELATION WITH MATERNAL DIABETIC VASCULAR COMPLICATIONSThe Lancet, 1964