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J Cell Mol Med. 2019 Jan;23(1):610-618. doi: 10.1111/jcmm.13966. Epub 2018 Nov 8.

Gestational age-dependent gene expression profiling of ATP-binding cassette transporters in the healthy human placenta.

Author information

1
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
2
Laboratory of Translational Endocrinology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
3
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
4
Division of Human Reproduction, Department of Obstetrics and Gynecology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
5
Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada.
6
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
7
Department of Obstetrics & Gynecology and Department of Cellular & Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
8
Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Brazil.

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.

KEYWORDS:

ABC transporters; ABCA6; gestational-age; lipid transporter; placenta

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