Regulation of Placental Efflux Transporters during Pregnancy Complications.

Abstract

The placenta is essential for regulating the exchange of solutes between the maternal and fetal circulations. As a result, the placenta offers support and protection to the developing fetus by delivering crucial nutrients and removing waste and xenobiotics. ATP-binding cassette transporters, including multidrug resistance protein 1, multidrug resistance-associated proteins, and breast cancer resistance protein, remove chemicals through active efflux and are considered the primary transporters within the placental barrier. Altered transporter expression at the barrier could result in fetal exposure to chemicals and/or accumulation of xenobiotics within trophoblasts. Emerging data demonstrate that expression of these transporters is changed in women with pregnancy complications, suggesting potentially compromised integrity of placental barrier function. The purpose of this review is to summarize the regulation of placental efflux transporters during medical complications of pregnancy, including 1) placental inflammation/infection and chorioamnionitis, 2) hypertensive disorders of pregnancy, 3) metabolic disorders including gestational diabetes and obesity, and 4) fetal growth restriction/altered fetal size for gestational age. For each disorder, we review the basic pathophysiology and consider impacts on the expression and function of placental efflux transporters. Mechanisms of transporter dysregulation and implications for fetal drug and toxicant exposure are discussed. Understanding how transporters are up- or downregulated during pathology is important in assessing possible exposures of the fetus to potentially harmful chemicals in the environment as well as the disposition of novel therapeutics intended to treat placental and fetal diseases. SIGNIFICANCE STATEMENT: Diseases of pregnancy are associated with reduced expression of placental barrier transporters that may impact fetal pharmacotherapy and exposure to dietary and environmental toxicants.

• Authors: Danielle Kozlosky, Emily Barrett, Lauren M Aleksunes
• Journal: Drug metabolism and disposition: the biological fate of chemicals (Drug Metab Dispos) Vol. 50 Issue 10 Pg. 1364-1375 (10 2022) ISSN: 1521-009X [Electronic] United States
• PMID: 34992073 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics.

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters
• Membrane Transport Proteins
• Multidrug Resistance-Associated Proteins
• Neoplasm Proteins
• Xenobiotics

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• ATP Binding Cassette Transporter, Subfamily G, Member 2 (metabolism)
• ATP-Binding Cassette Transporters (metabolism)
• Female
• Humans
• Membrane Transport Proteins (metabolism)
• Multidrug Resistance-Associated Proteins (metabolism)
• Neoplasm Proteins (metabolism)
• Placenta (metabolism)
• Pregnancy
• Pregnancy Complications
• Xenobiotics (metabolism)