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Int. J. Mol. Sci. 2018, 19(8), 2334; https://doi.org/10.3390/ijms19082334

Novel Insights into Concepts and Directionality of Maternal–Fetal Cholesterol Transfer across the Human Placenta

1
Institute of Biochemistry and Molecular Medicine, Faculty of Medicine, University of Bern, CH-3012 Bern, Switzerland
2
Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, CH-3012 Bern, Switzerland
3
Department of BioMedical Research, University of Bern, CH-3012 Bern, Switzerland
*
Author to whom correspondence should be addressed.
Received: 6 June 2018 / Revised: 14 July 2018 / Accepted: 23 July 2018 / Published: 9 August 2018
(This article belongs to the Special Issue Cholesterol and Lipoprotein Metabolism)
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Abstract

Cholesterol is indispensable for cellular membrane composition and function. It is also a precursor for the synthesis of steroid hormones, which promote, among others, the maturation of fetal organs. A role of the ATP-binding-cassette-transporter-A1 (ABCA1) in the transport of maternal cholesterol to the fetus was suggested by transferring cholesterol to apolipoprotein-A-1 (apo-A1), but the directionality of the apoA-1/ABCA1-dependent cholesterol transport remains unclear. We isolated primary trophoblasts from term placentae to test the hypotheses that (1) apoA-1/ABCA1 dispatches cholesterol mainly towards the fetus to support fetal developmental maturation at term, and (2) differentiated syncytiotrophoblasts (STB) exert higher cholesterol transport activity than undifferentiated cytotrophoblasts (CTB). As experimental models, we used (1) trophoblast monolayers grown on Transwell® system consisting of apical (maternal-like) and basal (fetal-like) compartments, and (2) trophoblasts grown on conventional culture plates at CTB and STB stages. Surprisingly, apoA-1-mediated cholesterol efflux operated almost exclusively at the apical-maternal side, where ABCA1 was also localized by immunofluorescence. We found greater cholesterol efflux capacity in STB, which was increased by liver-X-receptor agonist treatment and decreased by ABCA1 inhibition. We conclude that at term the apoA-1/ABCA1 pathway is rather involved in cholesterol transport to the mother than in transfer to the fully developed fetus. View Full-Text
Keywords: ABC transporter; cholesterol; fetal development; pregnancy; trans-placental transport; trophoblasts ABC transporter; cholesterol; fetal development; pregnancy; trans-placental transport; trophoblasts
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Kallol, S.; Huang, X.; Müller, S.; Ontsouka, C.E.; Albrecht, C. Novel Insights into Concepts and Directionality of Maternal–Fetal Cholesterol Transfer across the Human Placenta. Int. J. Mol. Sci. 2018, 19, 2334.

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