Induced cell injury and cell death as a cause of congenital malformations in rats.
Embryopathy has been produced by inhibition of histiotrophic nutrition in the rat using a number of agents which prevent this process. The experiments were carried out in vitro at various stages of development before the inception of a chorio allantoic placenta. Dose-dependent effects on the embryo were demonstrated using the acid bisazo dye Trypan Blue, which inhibits endocytosis, and an enzyme inhibitor of bacterial origin known as leupeptin which inhibits cathepsin B, H and L. Homogenates of rat kidney and placenta also produced congenital defects; the concommitant electron microscopical changes in the yolk sac suggest that these effects too are due to alterations in the availability or quality of histiotroph.
D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000818:Animals; D002403:Cathepsins / Q000037:antagonists & inhibitors; D002470:Cell Survival; D000013:Congenital Abnormalities / Q000209:etiology / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D007668:Kidney / Q000473:pathology; D007976:Leupeptins / Q000633:toxicity*; D008854:Microscopy, Electron; D009842:Oligopeptides / Q000633:toxicity*; D010920:Placenta / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D014343:Trypan Blue / Q000633:toxicity*; D015017:Yolk Sac / Q000473:pathology
D007976:Leupeptins; D009842:Oligopeptides; D002403:Cathepsins; D014343:Trypan Blue; C032854:leupeptin