ArticleDrug metabolism and disposition: the biological fate of chemicals2013
Gestational age-dependent changes in gene expression of metabolic enzymes and transporters in pregnant mice.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.
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32 citing papers in PubMed, 59 citations in OpenAlex.
- Evolving role of mitochondrial dysfunction and mitophagy in necrotizing enterocolitis.Pediatric research · 2026Article
- Impact of sex and pregnancy on hepatic CYP3A4 expression and activity in a humanized mouse model.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Estrogen associations with human pregnancy related increases in cytochrome P450 3A activity.Frontiers in pharmacology · 2025Article
- SLC20a1/PiT-1 is required for chorioallantoic placental morphogenesis.Vascular biology (Bristol, England) · 2023Article
- Maternal and Fetal Expression of ATP-Binding Cassette and Solute Carrier Transporters Involved in the Brain Disposition of Drugs.Advances in experimental medicine and biology · 2023Article
- Testing of drugs using human feto-maternal interface organ-on-chips provide insights into pharmacokinetics and efficacy.Lab on a chip · 2022Article
- An update on the physiologic changes during pregnancy and their impact on drug pharmacokinetics and pharmacogenomics.Journal of basic and clinical physiology and pharmacology · 2022Review
- Impact of pregnancy related hormones on drug metabolizing enzyme and transport protein concentrations in human hepatocytes.Frontiers in pharmacology · 2022Article
- The Impact of Pregnancy on Antihypertensive Drug Metabolism and Pharmacokinetics: Current Status and Future Directions.Expert opinion on drug metabolism & toxicology · 2021Review
- Efflux transporters in rat placenta and developing brain: transcriptomic and functional response to paracetamol.Scientific reports · 2021Article
- Article
- Sources of Interindividual Variability.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Pregnancy-Related Hormones Increase Nifedipine Metabolism in Human Hepatocytes by Inducing CYP3A4 Expression.Journal of pharmaceutical sciences · 2021Article
- 2,4,6-Tribromophenol Disposition and Kinetics in Pregnant and Nursing Sprague Dawley Rats.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Impact of Microbiome on Hepatic Metabolizing Enzymes and Transporters in Mice during Pregnancy.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Glucuronidation as a metabolic barrier against zearalenone in rat everted intestine.The Journal of veterinary medical science · 2020Article
- Impact of Viral Inflammation on the Expression of Renal Drug Transporters in Pregnant Rats.Pharmaceutics · 2019Article
- Temporal transcriptomic analysis of metabolic genes in maternal organs and placenta during murine pregnancy.Biology of reproduction · 2018Article
- The Placental Barrier: the Gate and the Fate in Drug Distribution.Pharmaceutical research · 2018Review
- Quantitative Proteomics Reveals Changes in Transporter Protein Abundance in Liver, Kidney and Brain of Mice by Pregnancy.Drug metabolism letters · 2018Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Pregnancy-induced changes in drug pharmacokinetics can be explained by changes in expression of drug-metabolizing enzymes and transporters and/or normal physiology. In this study, we determined gestational age-dependent expression profiles for all metabolic enzyme and transporter genes in the maternal liver, kidney, small intestine, and placenta of pregnant mice by microarray analysis. We specifically examined the expression of genes important for xenobiotic, bile acid, and steroid hormone metabolism and disposition, namely, cytochrome P450s (Cyp), UDP-glucuronosyltranserases (Ugt), sulfotransferases (Sult), and ATP-binding cassette (Abc), solute carrier (Slc), and solute carrier organic anion (Slco) transporters. Few Ugt and Sult genes were affected by pregnancy. Cyp17a1 expression in the maternal liver increased 3- to 10-fold during pregnancy, which was the largest observed change in the maternal tissues. Cyp1a2, most Cyp2 isoforms, Cyp3a11, and Cyp3a13 expression in the liver decreased on gestation days (gd) 15 and 19 compared with nonpregnant controls (gd 0). In contrast, Cyp2d40, Cyp3a16, Cyp3a41a, Cyp3a41b, and Cyp3a44 in the liver were induced throughout pregnancy. In the placenta, Cyp expression on gd 10 and 15 was upregulated compared with gd 19. Notable changes were also observed in Abc and Slc transporters. Abcc3 expression in the liver and Abcb1a, Abcc4, and Slco4c1 expression in the kidney were downregulated on gd 15 and 19. In the placenta, Slc22a3 (Oct3) expression on gd 10 was 90% lower than that on gd 15 and 19. This study demonstrates important gestational age-dependent expression of metabolic enzyme and transporter genes, which may have mechanistic relevance to drug disposition in human pregnancy.
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