Placental toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a well-known model substance for inducing in humans and monkeys a severe extrapyramidal syndrome similar to Parkinson's disease. The neurotoxic action of MPTP can be exerted not only in adult animals but also during fetal development by diaplacental passage. Here we show that, during the gestation period of mice, the placenta is another important target organ of MPTP cytotoxicity. Pregnant NMRI mice on gestation day 15 received a single intraperitoneal dose of 20, 40, or 60 mg/kg MPTP. Developmental parameters of the fetuses and the placentas were determined on gestation day 18. Placental weight was consistently reduced in all experimental groups. Histology showed conspicuous alterations of the labyrinth layer; at 20 mg/kg MPTP there was already a significant reduction of the trabecular diameters and from 40 mg/kg onwards, severe necrosis of the syncytial trophoblast cells. In addition, there were necrotic alterations of the cells of the visceral yolk sac. The toxic effects are confined to the placenta at the doses used in the present experiments, leading at just 60 mg/kg to a marked placental insufficiency syndrome.
Schmahl
W
W
Institut für Pathologie, GSF München, Neuherberg, Germany.
Usler
B
B
D000014:Abnormalities, Drug-Induced; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D020267:MPTP Poisoning; D051379:Mice; D009336:Necrosis; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000187:drug effects*; D010927:Placental Insufficiency / Q000139:chemically induced*; D011247:Pregnancy; D013047:Specific Pathogen-Free Organisms; D015017:Yolk Sac / Q000187:drug effects