Phenytoin-Induced Alterations Of Early Embryonic Gene Expression

Abstract

Since teratogen-induce congenital malformations are likely to result from changes in programmed gene expression, we have monitored the level of expression of a population of 20 candidate genes in order to identify any potentially altered patterns of gene expression occurring secondary to in utero phenytoin exposure that may contribute to the pathogenesis of the observed defects. This was accomplished using two newly developed procedures, in situ transcription and anti-sense RNA amplification (RT/ aRNA) technology. Quantification of the hybridization intensity of the aRNA probes generated through these procedures from gestational day 9:12 and day 10:0 embryos to cDNA clones of the selected candidate genes on slot blots allowed the relative abundance of the mRNAs of interest to be measured and statistically analyzed. Fluctuations in mRNA population levels during embryogenesis following maternal phenytoin exposure were monitored. This study provides the first composite examination of the coordinate changes in mRNA abundance for twenty candidate genes that may contribute to abnormal development resulting in phenytoin-induced congenital malformations.