Mouse placenta: hemodynamics in the main maternal vessel and histopathologic changes induced by 2-methoxyethanol and 2-methoxyacetic acid following maternal dosing.
The two main maternal vessels that are a major, if not the entire, source of maternal blood for the mouse placenta are unique in possessing intraluminal valvular projections. The morphologic configuration of these projections suggests their potential to converge, diverge, and rotate blood currents flowing under systolic pressure. The intravascular occurrence of circular fibrin bodies composed of concentric fibrin strands coagulated from the plasma and almost no blood cellular elements in these strands lends credence to this concept. Histopathologic changes in the extraembryonic and embryonic tissues induced by an intraperitoneal injection of 250 or 500 mg/kg of 2-methoxyethanol, or its metabolite, 2-methoxyacetic acid, via oral gavage were determined 48 hr after dosing CD-1 mice on day 11 of pregnancy. Both compounds caused 1) marked congestion and dilatation, associated with or without fibrinous occlusions, of the main maternal vessel of the placenta, 2) serosanguinous exudation and maternal hemorrhages from the placental periphery, 3) necrosis and desquamation involving the mesometrial surface or peripheral edge of the placenta, 4) translabyrinthine embryonic hemorrhage into the maternal circulation, and 5) embryonic hemorrhages into the exocoelomic, amniotic, and pericardial cavities. These lesions signify a disordered maternal circulation in the placenta suggestive of potentially serious pathologic effects. These lesions may play a role in the resorption, reduction in fetal body weight, and syndactyly or oligodactyly attributed to 2-methoxyethanol and 2-methoxyacetic acid.
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Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Protection Branch, Health and Welfare Canada, Ottawa, Ontario.
D000085:Acetates / Q000633:toxicity*; D000818:Animals; D005026:Ethylene Glycols / Q000633:toxicity*; D005260:Female; D005315:Fetal Diseases / Q000139:chemically induced; D005337:Fibrin / Q000032:analysis; D006439:Hemodynamics / Q000187:drug effects; D006470:Hemorrhage / Q000139:chemically induced; D051379:Mice / Q000033:anatomy & histology*; D010920:Placenta / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000139:chemically induced; D012039:Regional Blood Flow / Q000187:drug effects; D014592:Uterine Hemorrhage / Q000139:chemically induced
D000085:Acetates; D005026:Ethylene Glycols; D005337:Fibrin; C005219:methyl cellosolve; C013598:methoxyacetic acid