Altered activities of CYP1A1 and CYP19A1 enzymes in women using SSRI medication during pregnancy
Heidi Sahlman, Anna Itkonen, Marko Lehtonen, Leea Keski‐Nisula, Jaana Rysä
Abstract
INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) are commonly used medication for the treatment of depression during pregnancy. Their use may affect various biological molecules such as enzymes which regulate placental hormonal production and xenobiotic metabolism. Our aim was to investigate the effect of maternal SSRI use on activities of three placental enzymes. METHODS: We analyzed activities of xenobiotic metabolism enzymes cytochrome P450 1A1 (CYP1A1), aromatase (CYP19A1), and glutathione-S-transferase (GST) from placental microsomal and cytosolic subcellular fractions. Term placentas were collected from 47 SSRI users and 49 control women participating Kuopio Birth cohort (KuBiCo) during the years 2013-2015. Among SSRI users, escitalopram was the most widely used SSRI medication. RESULTS: The mean enzyme activities of all studied enzymes were lower in SSRI users compared to controls. A statistically significant difference was observed in the enzyme activities of CYP19A1 (p = 0.001) and CYP1A1 (p = 0.002) between the study groups after adjusting for use of additional medication, gestational diabetes, sex of the newborn and gestational weeks at delivery. SSRI use had no significant effect on placental GST enzyme activity. DISCUSSION: Our results indicate that SSRI medication alters placental enzyme activities. This may lead disturbances in maternal steroid hormone balance as well as in xenobiotic metabolism and may provide risk for both developing fetus and pregnant women.