Inhibition of yolk sac function in late gastrulation rat conceptuses as a cause of teratogenesis: an in vivo/in vitro study.

A rabbit anti-rat yolk sac antiserum, administered by intraperitoneal injection at 0.25 mL/100 g bodyweight into 8.5-day pregnant rats, resulted in a resorption incidence of 20%, and growth retardation and malformation of all surviving fetuses at term. In all subsequent experiments, pregnant rats either received this same dose of antiserum at 8.5 days or were untreated. When 9.5-day rat conceptuses were cultured for 48 h in a medium containing serum from a 9.5-day pregnant rat that had been treated with antiserum, development was severely abnormal, regardless of whether conceptuses were explanted from antiserum-treated or untreated dams. In contrast, culture for 48 h in serum from untreated 9.5-day pregnant rats resulted in normal growth and development of conceptuses explanted from untreated dams, and in slight growth retardation and dysmorphogenesis in 9.5-day conceptuses explanted from antiserum-treated dams. In the former, development was similar to that attained by 11.5-day conceptuses from untreated dams; in the latter, development was appreciably better than in 11.5-day conceptuses from antiserum-treated dams. These results indicate that the critical period of exposure of embryos in utero to teratogenic antiserum after administration to the 8.5-day pregnant rat is longer than 24 h and that a significant insult is delivered to the conceptus before 9.5 days ea. Using 9.4-day ea conceptuses in culture, pinocytosis (uptake of 125I-labelled polyvinylpyrrolidone) by the yolk sac, and its inhibition by antiserum, was demonstrated. No pinocytic activity was evident in the embryo itself. These data support the hypothesis that anti-yolk sac antiserum exerts its teratogenic action by inhibiting the nutritional function of the yolk sac during early organogenesis.