1279 SPECIFICITY OF RAT YOLK SAC ANTIBODIES IN PRODUCING CONGENITAL MALFORMATIONS, EMBRYONIC MALNUTRITION AND REDUCED PINOCYTOSIS

Abstract

In a series of experiments first published in 1961, we reported that antibodies prepared against rat kidney were potent teratogenic agents when administered to pregnant rats (Brent 1961). It was determined that antisera which were teratogenic localized in the developing yolk sac (Slotnick and Brent, 1966). Antisera prepared against VYS proved to be the most potent teratogens, and these teratogenic antisera reduced the endocytic uptake of proteins by the VYS (Brent et al, 1972, Freedman et al, 1983). Utilizing isolectric focusing techniques, various proteins were isolated from the VYS and antisera were prepared against these individual proteins. A large number of antisera were not teratogenic and did not localize in the developing yolk sac. A smaller group of antisera were found to localize in the VYS These antisera were studied with several techniques: Determination of the endocytic index utilizing (14C) sucrose, in vivo yolk sac localization utilizing fluorescent labelled antibody and teratogenic potency. It was found that yolk sac localization of antibody specific for yolk sac antigens does not prove that the antibodies have teratogenic potency. On the other hand, if the antibodies also reduce the endocytic index, then the antibodies will invariably have teratogenic potency. Thus, the reduction of endocytosis is the first method of accurately predicting teratogenic potential without having to perform time-consuming in vivo bioassays.