Quantitative analysis of Cyp1a2 expression and temporal characterization of zonation structure formation during mouse liver development.

Asthma attacks during pregnancy can cause inadequate oxygen supply to the fetus because the mother cannot get enough oxygen into her bloodstream. Even during pregnancy, medication such as theophylline is needed to avoid asthma seizure. Theophylline is metabolized by (Cytochrome P450) CYP1A2 in the maternal liver. On the other hand, whether theophylline transferred from the mother to the fetus is metabolized in its liver depends on the degree of CYP1A2 expression, but no such information is available. In the adult liver, CYP1A2 forms zonation structures to efficiently metabolize drugs and foreign substances. In this study, we quantitatively analyzed the expression levels of mCyp1a2 mRNA and protein in the liver throughout development, from fetal and neonatal stages to adulthood, while distinguishing between males and females. In addition, to determine the timing of the mCyp1a2 zonation, analysis was performed in fetal and neonatal livers. We found that mCyp1a2 males and females express very little mCyp1a2 in the fetal liver. One week after birth, mCyp1a2 protein expression was 24% and 14% of adult expression in males and females, respectively. Furthermore, the expression level of mCyp1a2 in both sexes was almost the same as that of adults after 28 days of age. In addition, they found that the zonation of mCyp1a2 begins to form 5 days after birth. It was found that mCyp1a2 expression is very low in the fetal liver, while the liver of a 14-day-old (P14) has approximately half the drug-metabolizing capacity compared to that of an adult liver.