Preterm Birth Associates With Increased Placental Expression of MDR Transporters Irrespective of Prepregnancy BMI

J Clin Endocrinol Metab. 2022 Mar 24;107(4):1140-1158. doi: 10.1210/clinem/dgab813.

Abstract

Context: Preterm birth (PTB) and suboptimal prepregnancy body mass index (BMI) operate through inflammatory pathways to impair fetoplacental development. Placental efflux transporters mediate fetal protection and nutrition; however, few studies consider the effect of both PTB and BMI on fetal protection. We hypothesized that PTB would alter the expression of placental multidrug resistance (MDR) transporters and selected proinflammatory cytokines, and that maternal underweight and obesity would further impair placental phenotype.

Objective: To determine whether placental MDR transporters P-glycoprotein (P-gp, encoded by ABCB1) and breast cancer resistance protein (BCRP/ABCG2), and proinflammatory cytokine levels are altered by PTB and maternal BMI.

Methods: A cross-sectional study was conducted to assess the effect of PTB (with/without chorioamnionitis), or the effect of maternal prepregnancy BMI on placental MDR transporter and interleukin (IL)-6 and -8 expression in 60 preterm and 36 term pregnancies.

Results: ABCB1 expression was increased in preterm compared to term placentae (P = .04). P-gp (P = .008) and BCRP (P = .01) immunolabeling was increased among all preterm compared to term placentae, with P-gp expression further increased in preterm pregnancies with chorioamnionitis (PTC, P = .007). Placental IL-6 mRNA expression was decreased in PTC compared to term placentae (P = .0005) and PTC associated with the greatest proportion of anti-inflammatory medications administered during pregnancy. Maternal BMI group did not influence placental outcomes.

Conclusion: PTB and infection, but not prepregnancy BMI, alter placental expression of MDR transporters and IL-6. This may have implications for fetal exposure to xenobiotics that may be present in the maternal circulation in pregnancies complicated by PTB.

Keywords: inflammation; multidrug resistance (MDR) transporters; obesity; placenta; preterm birth; underweight.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism
  • Body Mass Index
  • Chorioamnionitis* / metabolism
  • Cross-Sectional Studies
  • Cytokines / metabolism
  • Drug Resistance, Multiple
  • Female
  • Humans
  • Infant, Newborn
  • Interleukin-6 / metabolism
  • Neoplasm Proteins / metabolism
  • Placenta / metabolism
  • Pregnancy
  • Premature Birth* / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Cytokines
  • Interleukin-6
  • Neoplasm Proteins