Inhibitory effects of nephrotoxic antisera on the growth of rat fetuses

Vaillancourt, P.; McCallion, D. J.

doi:10.1016/0002-9378(72)90068-3

Cited by 12 publications

(4 citation statements)

References 13 publications

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“…The appearance of birth defects after injection of heterologous antiserum directed against whole rat kidney homogenate into pregnant rats during the organogenetic period was first reported by Brent and his colleagues (I). This finding has been repeatedly confirmed and extended by other investigators (2)(3)(4)(5)(6). The underlying mechanism whereby teratogenic kidney antiserum induces abnormal embryonic development is not understood, although the responsible teratogenic agents are immunoglobulin G (7).…”

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confidence: 66%

Isolation, partial characterization, and localization of a rat renal tubular glycoprotein antigen. Antibody-induced birth defects.

Leung¹

1982

The Journal of Experimental Medicine

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A glycoprotein with an apparent 340,000 mol wt (gp 340K) was isolated from rat kidney saline-soluble extract by ammonium sulfate precipitation, DE 52 ion-exchange cellulose chromatography, concanavalin A affinity column, Sephacryl S-300 gel filtration, and discontinuous polyacrylamide gel electrophoresis (PAGE). The relative purity of gp 340K was examined by double immunodiffusion analysis, disc PAGE, and immunoelectrophoresis. Injection of rabbit gp 340K antiserum into pregnant rats during the organogenetic period induced abnormal embryonic development, fetal growth retardation, and embryonic death. Antiserum against the immunocomplexes isolated by immobilized protein A also produced the same embryotoxic effects. The biologic effects of the antisera appeared to be dose dependent. Defects such as anophthalmia, hydrocephaly, exencephaly, cleft palate, cleft lip, and some cardiovascular anomalies were observed. The most frequently observed anomaly was anophthalmia. Immunofluorescent localization studies indicated that gp 340K antibodies localized in vivo in the visceral yolk-sac endodermal cells and the embryonic endoderm. In vitro immunofluorescent localization studies revealed that gp 340K was a component of the renal tubular cells that cross-reacted with antigen in the visceral yolk-sac endodermal cells and embryonic endoderm. The underlying mechanism whereby gp 340K antibodies induce birth defects is not known. Three hypotheses were discussed.

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supporting

confidence: 66%

Isolation, partial characterization, and localization of a rat renal tubular glycoprotein antigen. Antibody-induced birth defects.

Leung¹

1982

The Journal of Experimental Medicine

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“…This finding has been repeatedly confirmed and extended by other investigators (1,7,10,23,31). It was later demonstrated that the antiserum directed against rat chorioallantoic placenta (5) was also teratogenic and ;he placental antigens involved were glycoproteins (16).…”

Section: Discussionsupporting

confidence: 63%

Antiserum to Rat Visceral Yolk Sac Endoderm Induced Abnormal Embryonic Development

Leung

1983

Pediatr Res

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SummaryThe induction of abnormal embryonic development by heterologous tissue antisera has been well established. The underlying mechanism whereby such teratogenesis occurs is not known. There were implications that visceral yolk sac endoderm might be involved. Endoderm was isolated from rat visceral yolk sac of 14th day of gestation using a nonenzymic procedure. The purity of the endoderm preparation was examined by electron microscopy. The preparation contained sheets of single lager of endodermal cells with no apparent contamination by the underlying mesenchyme or basal lamina. The s~ecificitv of the antiserum was examined bv in vitro immunofluorescent localization studies. The antibodies against the endoderm localized only in the endodermal cells and some of the renal tubular cells. Intraperitoneal injection of the endoderm antiserum into Pday pregnant rats resulted in congenital malformation, embryonic death, and fetal growth retardation. The effects of the antiserum were dose-dependent. The most frequently observed defects were anophthalmia and microphthalmia. Retarding effect of the antiserum on the growth of the embryo at the egg cylinder stage was also observed. In vivo immunofluorescent localization studies indicated that the endoderm antibodies localized only in the endodermal cells of the visceral yolk sac placenta; no localization was observed in the visceral yolk sac mesenchyme, basal lamina, Reichert's membrane, maternal kidney tissue or the embryo proper. Abbreviations FITC, fluorescein isothiocyanate RM, Reichert's membrane VYS, visceral yolk sacThe appearance of malformations in the offspring after intraperitoneal injection of rabbit antiserum directed against whole rat kidney homogenate into 9-day pregnant rats was first reported by Brent et al. (6). This finding has been repeatedly confirmed and extended by other investigators (1, 7, 10,23,31). It was later demonstrated that the antiserum directed against rat chorioallantoic placenta (5) was also teratogenic and ;he placental antigens involved were glycoproteins (16). On the other hand, antisera to rat collagen (19), alpha-fetoprotein (22), renal glomerular basement membrane (21), whole serum, erythrocyte, spleen, brain, muscle and skin (6) seemed to have little effect on embryonic development when they were similarly injected into pregnant rats during the organogenetic period. Although the mechanism whereby teratogenic antisera induce abnormal embryonic development is not understood, immunofluorescent studies demonstrated that the antibodies of teratogenic antisera localized in vivo in the cytoplasm of the visceral yolk sac (VYS) endodermal cells as well as in the maternal glomeruli (29,21). The absorption studies reported by Jensen et al. (13) utilizing antiserum against whole term VYS suggested that the localization of antibodies in the VYS endodermal cells might contribute to the cause of abnormal embryonic development. It seemed logical to determine whether antigens of the VYS endodermal cells were indeed capable of stimulating teratoge...

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“…These authors demonstrated that rabbit antiserum against rat kidney homogenate caused embryonic death and abnormalities in the offspring when the antiserum was injected into a pregnant rat during the organogenetic period. Many investigators confirmed and extended Brent's findings (David et al, 1963;Bragonier et al, 1970;Gebhardt et al, 1970;Barrow and Taylor, 1971;Vaillancourt and McCallion, 1972;Mikhailov, 1976). Slotnick and Brent (1966) later demonstrated that the injected teratogenic kidney antibodies localized in the maternal renal glomerular basement membrane, Reichert's membrane, and visceral yolk-sac (VYS) endodermal cells.…”

Section: Introductionmentioning

confidence: 82%

Teratogenic antibody internalization by rat visceral yolk‐sac endoderm in vitro: An ultrastructural colloidal gold tracer study

1988

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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 embryonic development when they are injected into pregnant rats during the period of organogenesis. It has been proposed that these antibodies may induce embryopathy 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 mechanism(s) in which specific teratogenic IgG may interfere 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. 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 micropinocytic vesicles. Within 30 min, an increasing proportion 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.(ABSTRACT TRUNCATED AT 250 WORDS)

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Inhibitory effects of nephrotoxic antisera on the growth of rat fetuses

Cited by 12 publications

References 13 publications

Isolation, partial characterization, and localization of a rat renal tubular glycoprotein antigen. Antibody-induced birth defects.

Isolation, partial characterization, and localization of a rat renal tubular glycoprotein antigen. Antibody-induced birth defects.

Antiserum to Rat Visceral Yolk Sac Endoderm Induced Abnormal Embryonic Development

Teratogenic antibody internalization by rat visceral yolk‐sac endoderm in vitro: An ultrastructural colloidal gold tracer study

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