The effect of teratogenic antiserum on yolk-sac function in rat embryos cultured in vitro.

The teratogenicity of rabbit anti-rat visceral yolk-sac antiserum, injected into pregnant rats at either 8-5 or 9-5 days of gestation, has been confirmed. Normal rabbit serum was found not to be teratogenic. When conceptuses from 9-5-day pregnant rats were cultured for 48 h in heat-denatured homologous serum, to which antiserum was added for the final (or the penultimate) 6 h of culture, embryonic development was normal. The protein contents of embryos and yolk sacs (at harvesting) were however decreased. When antiserum was present in cultures for the final 6 h, pinocytosis by the yolk sac, as measured by the uptake of l-labelled polyvinylpyrrolidone (PVP), was decreased to an extent related to the concentration of antiserum in the culture medium and to a minimum level of about 40%. The presence of antiserum in cultures for the penultimate 6 h only, with I-labelled PVP present for the final 6 h only, produced an identical result. No uptake of radioactivity into the embryo was observed, in either the absence or presence of antiserum. When conceptuses were cultured for the final 6 h in vitaminand glucose-supplemented dialysed homologous serum whose proteins were [H]leucine-labelled, the presence of antiserum for either the final or penultimate 6 h again resulted in a decrease in the uptake of radioactivity by conceptuses. Uptake of radioactivity into yolk sac and embryo was decreased by the same amount, indicating that proteolysis in yolk-sac lysosomes was not inhibited. In parallel control experiments in which normal rabbit serum replaced rabbit anti-rat visceral yolk-sac antiserum, no effects on embryonic development, on protein contents of yolk sacs and embryos at harvesting, or on the uptake of radioactivity by conceptuses were observed. These results are interpreted as providing evidence that teratogenic antibodies decrease pinocytosis of protein by visceral yolk sac at the early organogenesis stage and consequentially decrease the availability of amino acids and thus protein synthesis in both yolk sac and embryo. It is proposed that this effect constitutes the mechanism of action of teratogenic antisera.