The production of congenital malformations using tissue antisera. X. Effectiveness of kidney antigens treated with neuraminidase or trypsin

Abstract

Rabbit antineuraminidase-treated rat kidney and rabbit antitrypsin-treated rat kidney supernatant antisera were embryotoxic resulting in embryonic growth retardation, malformations, and death when injected into 15 pregnant rats. The same two antisera were also found to be nephrotoxic as manifested by their ability to induce proteinuria in 28 male rats. However, the antiserum against neuraminidase- treated rat kidney homogenate was significantly less nephrotoxic (averaging 46 mg urinary protein/24 hr) than the antiserum against the soluble supernatant obtained from trypsin-digested rat kidney homogenate (averaging 180 mg urinary protein/24 hr). The embryotoxic potency of these two antisera did not seem to correlate with their respective nephrotoxic potency. The less nephrotoxic antiserum, namely the antiserum against neuraminidase-treated rat kidney, is about five times as embryotoxic as that of the more nephrotoxic antiserum. Fluorescent-labeled antibody localization studies showed that the teratogenic antibodies localized in vivo in the maternal glomerular basement membrane, Reichert’s membrane, and the endodermal cells of the visceral yolk sac of the developing embryo. There were at least two bands of identity between antiserum against trypsin-treated kidney supernatant and antiserum against neuraminidase-treated kidney homogenate. The possible role played by Reichert’s membrane and the visceral yolk sac endodermal cells in teratogenesis induced by heterologous antibodies is discussed along with other relevant hypotheses. This study indicates that different antibodies may be involved in nephrotoxic serum nephritis and experimental production of congenital malformations induced by heterologous antirat kidney antiserum. Although some antibodies may be both nephrotoxic and embryotoxic, it is important to pursue the possibility that some antibodies may have embryotoxic effects without producing any nephrotoxicity. This possibility should be of most interest to the experimental embryologists and those interested in experimental methods of interrupting pregnancy. © 1972 International Pediatric Research Foundation, Inc.