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Cited by 51Pharmacogenetics and Drug MetabolismDrug-Induced Hepatotoxicity and ProtectionDrug Transport and Resistance Mechanisms

Differences in cytochrome p450 enzyme expression and activity in fetal and adult tissues

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Robinson, Joshua F., Hamilton, Emily G., Lam, Juleen, Chen, Hao, Woodruff, Tracey J.·2020·Placenta
DOI 10.1016/j.placenta.2020.07.009PMC PMC8021394
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Abstract

Introduction Human cytochrome p450 (CYP) enzyme expression and activity is lower in the fetus as compared to the adult; however, limited quantitative data exists regarding the specific differences in magnitude or the degree of inducibility due to environmental factors. Methods We utilized a combination of in silico- and molecular-based approaches to profile and compare CYP expression/activity in human adult liver and fetal tissues. Using public datasets, we evaluated human CYP expression between: 1) placenta vs. adult livers; 2) fetal vs. adult livers; or 3) five compartments of the human placenta. We generated new experimental data, characterizing expression levels of nine CYPs in placenta/fetal liver vs. adult liver. In a subset of samples, we evaluated CYP3A4 activity. Finally, we summarized evidence of human fetal CYP expression/activity and environmental exposures during pregnancy. Results In silico, CYPs were predominately expressed at higher levels in the adult liver vs. fetal tissues, with a few noted exceptions. Sixty percent of CYP enzymes were expressed at nominal levels in the placenta. In wet-lab analyses, we observed significant CYP-specific differences in expression/activity between adult and fetal tissues; CYP2E1 and -3A4 were expressed significantly lower in fetal vs. adult livers, while CYP2J2 levels were similar. Discussion We provide a qualitative review of the expression of the CYP enzyme family in critical sites of xenobiotic distribution during human pregnancy and novel quantitative data regarding fetal CYP expression and activity during mid-gestation. Data outputs may be a resource for modeling predictions of chemical distribution and sensitivity.

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  • Compared to adult liver, fetal liver is immature in its capacity to metabolize xenobiotics; it expresses a different set of xenobiotic-metabolizing enzymes, and the total amount of cytochrome P450 activity in fetal liver is significantly lower than in adult liver.

    “Compared to adult liver, fetal liver is immature in its capacity to metabolize xenobiotics; it expresses a different set of xenobiotic-metabolizing enzymes, and the total amount of cytochrome P450 activity in fetal liver is significantly lower than in adult liver (Hakkola et al., 1998; Robinson et al., 2020).”

    From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Robinson et al., 2020

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Cited by

Sorted by citations

Authors
Robinson, J. F., Hamilton, E. G., Lam, J., Chen, H., & Woodruff, T. J.
Affiliations
University of California, San Francisco (US)
Corresponding author
Robinson, Joshua F.
ORCID
Venue
Placenta
Publisher
Elsevier BV
Published
2020-10
Volume
100
Pages
35-44
ISSN
0143-4004 (ISSN-L)
DOI
10.1016/j.placenta.2020.07.009
PMC
PMC8021394
OpenAlex
W3047320223
Cited by
51
References
2
Citations by year
2026: 8 · 2025: 10 · 2024: 7 · 2023: 10 · 2022: 11 · 2021: 5
FWCI
5.78
Type
journal article
Language
en
Open access
Licence
Locations
  • Placenta (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • U.S. Environmental Protection Agency (RD 83543301, RD 83467801)
  • California Environmental Protection Agency
  • National Institute of Environmental Health Sciences (P20ES018135, R21ES022422, R00ES023846, P01ES022841)
  • National Institute of Child Health and Human Development (T32HD007263)
  • National Institute of General Medical Sciences (R01GM118122)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
cytochrome P450, fetal liver, CYP3A4, CYP2E1, CYP2J2, enzyme expression, enzyme activity, pregnancy, environmental exposure, human liver, developmental differences
MeSH terms
Aromatase, Computer Simulation, Environmental Exposure, Female, Fetus, Humans, Liver, Placenta, Pregnancy, Pregnancy Trimester, Second, Cytochrome P-450 CYP3A

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