The role of xenobiotic-metabolizing enzymes in the placenta: a growing research field

ABSTRACT

Introduction: The placenta is a temporary and unique organ that allows for the physical connection between a mother and fetus; this organ regulates the transport of gases and nutrients mediating the elimination of waste products contained in the fetal circulation. The placenta performs metabolic and excretion functions, on the basis of multiple enzymatic systems responsible for the oxidation, reduction, hydrolysis, and conjugation of xenobiotics. These mechanisms give the placenta a protective role that limits the fetal exposure to harmful compounds. During pregnancy, some diseases require uninterrupted treatment even if it is detrimental to the fetus. Drugs and other xenobiotics alter gene expression in the placenta with repercussions for the fetus and mother’s well-being.

Areas covered: This review provides a brief description of the human placental structure and function, the main drug and xenobiotic transporters and metabolizing enzymes, placenta-metabolized substrates, and alterations in gene expression that the exposure to xenobiotics may cause.

Expert opinion: Research should be focused on the identification and validation of biological markers for the assessment of the harmful effects of some drugs in pregnancy, including the evaluation of polymorphisms and methylation patterns in chorionic villous samples and/or amniotic fluid.

KEYWORDS:

• CYP450 enzyme
• drug
• gene expression
• placenta
• placental metabolism
• pregnancy
• transport protein

Article Highlights

• The placenta expresses diverse xenobiotic-metabolizing enzymes (XMEs) involved in the regulation of maternal and fetal exposure to hormones, dietary compounds, drugs, and environmental chemicals through biotransformation and elimination. The number and amount of expressed XMEs varies depending on the period of gestation and maternal age and health status.

• Apparently, all drugs cross the placenta and are metabolized by it to a certain extent through different mechanisms. Exposure to these substances can affect the expression of genes that encode XMEs and transporter proteins. Consequently, these alterations may provoke the deregulation of pregnancy and/or of fetal development.

• Advances in new technologies are expected to improve the treatment of maternal and fetal diseases during pregnancy.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by Instituto Politecnico Nacional-Mexico, SIP-20196451 and SIP-20196043.