Ocular changes in the mouse embryo following acute maternal ethanol intoxication.
The development of the eye was investigated in the mouse embryo following a single administration of ethanol plus [3H]thymidine to the dam on day 13 of gestation. After 1 hr there was no difference in the number of labelled cells/100 micron 2 in the neural layer of the retina compared to controls, but there was an alcohol-related reduction in labelling density. After 24 hr there was an increase in the numbers of both pyknotic cells and mitotic figures, breaks occurred in the inner surface of the retina and cell debris was being extruded into the posterior chamber. At 48 hr the increase in pyknotic cells persisted, but there was less evidence of cell debris and the borders had been repaired. The estimated cell cycle time in the neural progenitor cells following maternal alcohol administration was increased 7-fold compared to controls. Morphometric analysis revealed that after 48 hr there were significant alcohol-related reductions in the width and depth of the eye, in the thickness of the neural layer and in the interocular distance. It appears that many of the ophthalmic abnormalities reported in human fetal alcohol syndrome can be produced in the mouse embryo following a single episode of acute maternal intoxication during a critical period of ocular ontogeny, and that they evolve primarily from disturbances in the normal patterns of recruitment and loss of neural progenitor cells in the developing retina.
Kennedy
L A
LA
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Elliott
M J
MJ
D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D005123:Eye / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D005260:Female; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D051379:Mice; D011247:Pregnancy; D013936:Thymidine; D013997:Time Factors
D000431:Ethanol; D013936:Thymidine