Ultrastructural pathologic changes of rat extraembryonic visceral endodermal cells exposed to teratogenic antibodies in vivo.

It has been well established that certain heterologous tissue antibodies may induce abnormal embryonic development when injected into pregnant rodents during the organogenetic period. It has been postulated that these antibodies indirectly cause embryopathy by interfering with the normal functions of the yolk-sac placenta. The exact mechanism whereby these antibodies may induce placental pathology is not known. Specific teratogenic antibodies against a homogeneous rat kidney glycoprotein or a visceral yolk-sac glycoprotein antigen were injected intraperitoneally into 9th day pregnant rats. Electron microscopic examinations of the extraembryonic visceral endodermal cells of the egg cylinder were performed at 4, 6, 9, and 24 hours after the administration of the teratogenic antibodies. Control animals were injected with normal rabbit serum proteins. Extraembryonic visceral endodermal cells were similarly processed and examined as the experimental groups. The results seemed to indicate that the teratogenic antibodies induced increased autophagocytosis and morphologic changes associated with the phagolysosomes (secondary lysosomes) within the extraembryonic visceral endodermal cells at 9 hours following antibody administration. After 24 hours there was an apparent reduction or a complete disappearance of the supranuclear phagolysosome-like and lysosome-like structures, and the appearance of many large and small electron lucent vacuoles containing finely granular materials. Similar ultrastructural pathology was not observed in the 4 and 6 hour experimental and all of the control groups of animals. No other obvious intracellular or intercellular changes were observed in all of the experimental groups. Although the exact mechanism whereby the teratogenic antibodies may induce pathologic changes in the extraembryonic visceral endodermal cells remains to be determined, the present ultrastructural study demonstrated, for the first time, that teratogenic antibodies induced abnormal pathology in the extraembryonic visceral endodermal cells during the critical period of organogenesis.