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Previous work from our laboratory has demonstrated that specific rabbit immunoglobulins G (IgG) against a glycoprotein antigen of rat kidney proximal tubule or a cross-reacting visceral yolk-sac endodermal cell antigen will induce abnormal embry- onic development when they are injected into pregnant rats during the period of organogenesis. It has been proposed that these antibodies may induce embryopa- thy by interfering with functions of the visceral yolk- sac placenta, an important organ providing nutrients to the embryo at this stage of development. In order to gain some insight into the underlying pathogenic mech- anism(s) in which specific teratogenic I& may inter- fere with visceral yolk-sac functions, we examined the uptake of these teratogenic IgG by the visceral yolk-sac endodermal cells at the electron microscopic level. microscopic level. The results demonstrated that teratogenic rabbit IgG specifically localized on the fuzzy coat of the external apical cell membrane of the visceral yolk-sac endoderm at the intermicrovillous region. Within 5 min, the IgG were rapidly internalized via coated pits and micropi- nocytic vesicles. Within 30 min, an increasing propor- tion of gold particles appeared within uncoated vesicles or vacuoles of various sizes; most of the gold particles were in close proximity to the inner membranous lining of the vesicles. Similar findings were observed after 1- or 2-hr incubation. After 24- to 48-hr culture, however, the gold particles appeared to have dissociated from the inner surface of the vesicle membrane. For all the time points studied, gold particles were not observed in close association with the basal or lateral plasmalemma of the endodermal cells or in the connective tissue spaces and blood vessels of the visceral yolk-sac placenta. We interpret the results as follows: 1) the teratogenic rabbit IgGs interacted with their antigen on the apical plasma membrane of the visceral yolk-sac endodermal cells; 2) the teratogenic IgGs (coupled to their antigen) were internalized by endocytosis via coated pits; 3) the IgGs were later either hydrolyzed or dissociated from their antigen in uncoated vesicles or vacuoles; and 4) there was little or no evidence to indicate that the IgGs were transported between or across the endodermal cells to reach the embryo. It is postulated that the responsible antigen may be a receptor which plays an important role in transporting nutrient($ to the embryo. Specific polyclonal terato- genic

Passive Heymann nephritis (PHN) is an animal model of immune-complex-induced renal dis- ease resembling human membranous glomerulonephri- tis. It was induced in rats by injecting rabbit antiserum directed against glycoprotein antigens isolated from rat embryonic visceral yolk-sac microvilli (VYS-MV). The glycoprotein antigens were isolated by extracting the VYS-MV with detergent Nonidet P-40 followed by gel filtration in Sephacryl S-300 and finally by lectin affin- ity chromatography with Ricinus communis agglutinin I. In uitro immunofluorescent localization studies dem- onstrated that the nephritogenic antibodies were local- ized along the apical region of the visceral yolk-sac endodermal cells and the brush border of the proximal tubular cells of the kidney. Rats injected with a single dose of the antiserum manifested proteinuria. Indirect immunofluorescent studies showed that the injected rabbit IgG was localized in uiuo along the capillary walls of the glomerulus in a granular fashion. Electron microscopic examination of the same kidney glomeruli revealed numerous electron-dense deposits along the lamina rara externa of the glomerular basement mem- brane. Fusion of the epithelial foot processes was also present. These findings represent the typical immuno- pathological characteristics of Heymann nephritis. Furthermore, with the aid of Ouchterlony analysis, the antiserum against the isolated VYS antigens exhibited an immunoprecipitin band which was in common with that formed by the antiserum against the homogeneous nephritogenic antigen (gp330) of renal brush border or- igin. Thus, the nephritogenic antigens which have been found to be associated with the brush border of the renal proximal tubules may also be present or cross- reacted in the microvilli of the rat embryonic visceral yolk-sac.