Gene expression profiles of drug-metabolizing enzymes (DMEs) in rat liver during pregnancy and lactation

Abstract

A cDNA microarray analysis was conducted to examine hepatic gene expression profiles in pregnant and lactating F344 rats compared to a virgin control group using an Affymetrix GeneChip system. Of the approximately 16000 gene transcripts interrogated, more than 1000 were significantly modified in their expression when detected either in late pregnancy (19 days of gestation, GD 19, 513 genes upregulated and 579 downregulated) or on the day of delivery (postpartum 0 day, PPD 0, 497 upregulated and 733 downregulated). Particular interest was paid to the gene expression of drug-metabolizing enzymes (DMEs) and nuclear receptors (NRs). Though the expression of a few genes, those for CYP7A1, CYP51 and Sultx3, increased, the expression of a number of genes encoding DMEs (Phase I and Phase II) and NRs decreased during pregnancy and lactation. Changes in the expression of 9 genes encoding DMEs and NRs were confirmed by quantitative real-time PCR. For all 9 genes tested, overall, the results of the microarray and real-time PCR analyses were in agreement. This is the first application of a microarray analysis to the expression profiling of genes encoding DMEs and NRs in the liver of pregnant and lactating rats. When combined with other studies, the present study may provide a basis for investigating the mechanism of toxicity of environmental or other nonphysiologic chemicals to the fetus and mother and drug safety during pregnancy and lactation.