Abstract
Pregnant C3H mice were exposed to vitamin A on the 7th to 10th day after copulation. Fetuses were examined at 18 or 19 days gestation for gross abnormalities, and assayed for total brain acetylcholinesterase (EC 3.1.1.7., AChE) activity and choline acetyltransferase (EC 2.3.1.6., ChAT) activity. A dose-related increase in embryolethality was found after treatment with vitamin A on day 9. Earlier administration of vitamin A on day 7 or 8 was associated with a higher fetal mortality. A marked increase in the incidence of gross abnormalities was found with an increase in dose of the teratogen. Administration of 5,000 IU vitamin A on day 9 was not associated with an alteration in fetal weight, brain weight or brain AChE activity. Similarly, there was no change in brain weight or AChE activity after 10,000 IU on day 9, although fetal weight was reduced. The administration of 10,000 IU on day 10, however, was associated with an elevated brain AChE activity, but no alteration in fetal weight, brain total protein content, or brain ChAT activity. The increased brain AChE activity was due predominantly to an increase in one of the isoenzymes. The results indicate that an alteration in brain AChE activity depends on the dose and timing of administration of vitamin A, and does not necessarily correlate with morphological abnormalities, ChAT activity, or brain protein content.
Since x-irradiation and environmental contaminants such as carbamates and organophosphates may be teratogenic and affect adversely brain AChE activity following exposure to toxic amounts, these findings may also have a bearing on the toxicity to the fetus of agents other than vitamin A. Furthermore, the findings confirm the teratogenic potential of megadoses of vitamin A in the mouse fetus, a warning that also applies to humans, particularly with the increasing use of vitamin A and the retinoids.
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Pillans, P.I., Stephenson, B.A. & Folb, P.I. Vitamin A effects on fetal mouse cephalic acetylcholinesterase and choline acetyltransferase. Arch. Environ. Contam. Toxicol. 17, 665–671 (1988). https://doi.org/10.1007/BF01055836
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DOI: https://doi.org/10.1007/BF01055836