Intrauterine growth restriction (IUGR) is known to impact maternal and fetal Cytochrome P450 (CYP) activity, which may be mediated by increased reactive oxygen species (ROS) due to reduced oxygen status. This change in activity may impact intrauterine exposure to drugs, which presents both immediate and lifelong health risks for progeny. Pyrroloquinoline quinone (PQQ) has strong antioxidant properties and significant advantages over traditional antioxidants. This study aimed to evaluate the effects of antenatal PQQ administration on CYP activity in placenta and fetal liver of guinea pigs with spontaneous IUGR (SpIUGR).
Guinea pig dams were randomly assigned to two groups at 35 days gestational age (dGA): control and PQQ (0.18mg/kg/day administered in drinking water). Dams were humanely killed at 65 dGA (term, ~69 dGA), and fetuses were categorized based on fetal weight and brain to liver ratio, yielding four groups: Normal Growth (NG) ± PQQ and SpIUGR ± PQQ. Fetal liver and placental tissues were collected and prepared to assess CYP activity in vitro using functional assays.
Fetal body weight, liver weight and relative liver weight were lower in SpIUGR (all P<0.0001), as was the fetal-to-placental weight ratio (P=0.0143), while brain to liver ratio was higher (P<0.0001), irrespective of PQQ treatment. SpIUGR reduced CYP2D6 activity (P=0.0395) in the fetal liver, irrespective of PQQ treatment. Placental CYP2D6 was reduced in SpIUGR in the absence of PQQ treatment only (P=0.0422).
IUGR impairs CYP2D6 activity in fetal liver and placenta, an enzyme responsible for metabolizing 20-30% of drugs. Interestingly, PQQ treatment offered no restorative benefits to CYP2D6 activity in the IUGR fetal liver or placenta. This highlights a need to consider fetal growth when prescribing medications during pregnancy.