Gestational age‐dependent gene expression profiling ofATP‐binding cassette transporters in the healthy human placenta

Abstract

The ATP‐binding cassette (ABC) transporters control placental transfer of several nutrients, steroids, immunological factors, chemicals, and drugs at the maternal‐fetal interface. We and others have demonstrated a gestational age‐dependent expression pattern of two ABC transporters, P‐glycoprotein and breast cancer resistance protein throughout pregnancy. However, no reports have comprehensively elucidated the expression pattern of all 50 ABC proteins, comparing first trimester and term human placentae. We hypothesized that placental ABC transporters are expressed in a gestational‐age dependent manner in normal human pregnancy. Using the TaqMan® Human ABC Transporter Array, we assessed the mRNA expression of all 50 ABC transporters in first (first trimester, n = 8) and third trimester (term, n = 12) human placentae and validated the resulting expression of selected ABC transporters using qPCR, Western blot and immunohistochemistry. A distinct gene expression profile of 30 ABC transporters was observed comparing first trimester vs. term placentae. Using individual qPCR in selected genes, we validated the increased expression of ABCA1 (P < 0.01), ABCA6 (P < 0.001), ABCA9 (P < 0.001) and ABCC3 (P < 0.001), as well as the decreased expression of ABCB11 (P < 0.001) and ABCG4 (P < 0.01) with advancing gestation. One important lipid transporter, ABCA6, was selected to correlate protein abundance and characterize tissue localization. ABCA6 exhibited increased protein expression towards term and was predominantly localized to syncytiotrophoblast cells. In conclusion, expression patterns of placental ABC transporters change as a function of gestational age. These changes are likely fundamental to a healthy pregnancy given the critical role that these transporters play in the regulation of steroidogenesis, immunological responses, and placental barrier function and integrity.

Breast Cancer Resistance Protein (BCRP/ABCG2) Inhibits Extra Villous Trophoblast Migration: The Impact of Bacterial and Viral Infection

“…Significant down-regulation of BCRP (62.37%, Figure 2F) and ABCG2 (63.85%, Figure 2B) was observed following 48 h of si ABCG2 duplex treatment. Next, we determined the specificity of siRNA against ABCG2 by examining the mRNA levels of other related ABC transporters that are known to be expressed in trophoblasts: ABCB1 , ABCC2 , and ABCC3 [29]. The siRNA sequences were with unique specificity against ABCG2 mRNA.…”

Expression of severe acute respiratory syndrome coronavirus 2 cell entry genes, angiotensin-converting enzyme 2 and transmembrane protease serine 2, in the placenta across gestation and at the maternal-fetal interface in pregnancies complicated by preterm birth or preeclampsia

“…Placental tissue was sampled and processed as previously described. 29 Briefly, placental villous tissues from first-trimester pregnancies, following dilation and curettage, were visually identified and dissected from the decidua and other tissues, by specialized RCWIH staff. Second-and third-trimester placental villous tissues and placental fragments from PTB and PE pregnancies were dissected and harvested immediately after birth in a similar way.…”

Dysregulation of placental ABC transporters in a murine model of malaria-induced preterm labor

“…Among the ABC transporters, the best described are the ABC lipid transporter, ABCA1, and the ABC drug transporters, P‐glycoprotein (P‐gp, encoded by ABCB1 in humans and Abcb1a/Abcb1b in rodents), breast cancer resistance protein (BCRP, ABCG2 ) and the multidrug resistance‐associated proteins (MRPs‐2 and 5, ABCC2 and ABCC5 ). Physiological substrates of ABC transporters include: cholesterol, folic acid, steroid hormones and inflammatory mediators; whereas bisphenol A, many herbicides and pesticides, antibiotics, antiretrovirals and antidepressants represent nonphysiological substrates 13,14 . Thus, it is likely that altered placental ABC transporter expression caused by MiP could disturb the fetal biodisposition of these substrates with potentially significant effects on clinical outcomes.…”