Potential role of somatomedin inhibitors in the production of diabetic embryopathies

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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.