EXPRESSION OF RAT MICROSOMAL EPOXIDE HYDROLASE DURING PREGNANCY

Microsomal epoxide hydrolase (mEH) protein and messenger ribonucleic acid (mRNA) levels were assessed in maternal rats during pregnancy and mEH gene expression was compared with cytochrome P450 expression. Immunoblot analysis using goat anti-rat mEH antibody showed that hepatic mEH levels in adult rats at day 12 of gestation were comparable to those in virgin female rats at the same age, whereas mEH protein levels were substantially decreased by similar to 70% at day 20 of pregnancy. Northern and slot blot analyses revealed that hepatic mEH mRNA levels failed to be modulated at day 12 of pregnancy, whereas mEH mRNA levels were decreased to similar to 20% of virgin control in late pregnancy (i.e. day 20), which was consistent with the result of mEH immunoblot analysis. Hepatic cytochrome P4502E1 levels were also diminished at day 12 and day 20 of gestation by similar to 50% and similar to 70%, respectively, relative to virgin control rats, as supported by immunoblot analysis. Hepatic P4502E1 mRNA levels at day 12 and day 20 of pregnancy were also significantly decreased to 30% and 8% of virgin rats at 17 weeks of age, respectively, demonstrating that suppression in P4502E1 protein levels accompanied decreases in its mRNA expression. The levels of cytochrome P4501A2 mRNA at either day 12 or day 20 of pregnancy was decreased by similar to 50% relative to virgin female rats, which was less than that observed in mEH or P4502E1 expression. Pregnancy failed to affect P4501A1 mRNA levels, which were not detectable in female rats at 17 weeks of age. Renal mEH mRNA levels in maternal rats at day 20 of gestation were also decreased to 25% of virgin control. These results demonstrated that levels of mEH and P4502E1 proteins decreased significantly in late pregnancy with concomitant decreases in their mRNA levels.