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C.J. Calvano, R. LeFevre, R.M. Hoar, R.F. Mankes; Experimental prenatal therapy for oculo–cranial defects in a fetal alcohol syndrome (FAS) model . Invest. Ophthalmol. Vis. Sci. 2004;45(13):31.
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Purpose: In utero sex steroids modulate birth defects in FAS including low birth weight, microphthalmia, and craniofacial anomalies. We devised a prenatal maternal estradiol (E2) or testosterone (T) treatment to minimize growth related birth defects in a rodent model. Methods: Based on dose–ranging studies 6 groups of pregnant rats receiving control or alcoholic liquid diets were given 2 subcutaneous injections of vehicle (seaseme oil 1ml/kg), estradiol dipropionate (0.25 mg/kg) or testosterone propionate (0.5 mg/kg) on gestation day 18, a critical period for growth. Fetuses were examined on day 20 for growth delay / structural defects. Multicompartment sex steroid analysis was performed by radioimmunoassay. Results: Table 1 presents the effects of maternal sex steroid supplementation on fetal birth weight and anomaly incidence (data = mean +/– SEM *p<0.05 by t–test). T given to non–alcoholic controls resulted in a non–significant decrease in birth weight and increased anomalies. All other experimental groups had significant birth weight reduction and increased structural anomalies including delayed craniofacial ossification. Analysis of sex steroid levels (maternal, fetal, placental, amniotic) resulted in significant correlations between the number of abnormal pups per litter and : maternal estradiol (0.34), maternal progesterone (0.28), placental progesterone (0.55), fetal estradiol (0.33) and most strongly fetal progesterone (0.72). Conclusions: We expected steroid supplementation to modulate the fetal response to ethanol mediated injury as evidenced by birth weight and by the incidence of ocular and craniofacial anomalies. Based on assay of various pharmacokinetic compartments our data suggest that progesterone and the interconversion of steroids may be critical to fetal outcome. Previous E2 dependent patterns of microphthalmia and cranial–orbital ossification delay were not observed in this pilot study. Additionally, organ specific effects of the steroid supplements were not significant. The ideal agent and dosing regimen for prenatal treatment of specific anomalies remains elusive. Table 1:Effect of sex steroids on birth defects in FAS
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