This study was planned to investigate the effects of
ethanol on the
genetic susceptibility of the TO mouse to neural tube malformations and to determine the ameliorative effects, if any, of
aspirin a potent
prostaglandin inhibitor. The TO mouse exhibits a spontaneous incidence of 3.6%
exencephaly. The mice were exposed to single (i.p.) dose of 0.03 ml/gm
body weight of a
solution of (25%v/v) of
absolute alcohol in physiological saline on day 7 or 8 of gestation. Subteratogenic doses (150 or 200 mg/kg) of
aspirin were administered (i.p.) an hour before
ethanol exposure. Fetuses were collected on day 18 and compared with those of the untreated, and saline treated pair-fed pair-watered controls as well as with those of the
aspirin alone treatment group. A total of 175 litters were studied. Alcohol caused a three-fold increase against the background incidence of
exencephaly. Several craniofacial anomalies and growth retardation were also observed.
Alizarin red-S stained skeletal preparations revealed extensive malformations of the craniofacial skeleton in the exencephalic fetuses. Both doses of
aspirin administered prior to alcohol treatment significantly accentuated the alcohol-induced prenatal mortality. The rescue effect of
aspirin on alcohol-induced
intrauterine growth retardation was also significant although
fetal weight was not restored to levels comparable to those of the controls. Pre-treatment with
aspirin (both 150 and 200 mg/kg) on day 8 of gestation resulted in a numerical, though not statistically significant increase in alcohol-induced
exencephaly. On the other hand pre-administration of the lower dose on day 7
exencephaly. On the other hand pre-administration of the lower dose on day 7 of gestation caused a significant reduction while the higher dose gave rise to a significant increase in the incidence of this malformation.
Aspirin also reduced the frequency of alcohol-induced arched palate and the baseline
exencephaly. These data provide evidence for the possible interaction of alcohol with the
genetic susceptibility to
exencephaly in this strain of mice. The lack of a clear dose-dependent antagonistic effect of
aspirin on alcohol-induced
exencephaly suggests that the production of this malformation is probably not mediated by
prostaglandin as it was shown for limb and renal abnormalities (Randall, C.L., Anton, R.F. and Becker, H.C. (1991).
Aspirin dose dependently reduces alcohol induced
birth defects and
prostaglandin E levels in mice. Teratology 44, 521-529).