ABSTRACT
Membrane transporters are essential during pregnancy, being a core component of the exchange of nutrients, gases, and metabolic products between the mother and the developing fetus. Important compounds to be transported include vitamins and minerals, amino acids, glucose, as well as cholesterol. Cholesterol transport across the plasma membrane is mediated mainly by members of the ATP-binding cassette (ABC) transporter family. Cholesterol is present in every cell of the body, where it helps maintain the integrity of cell membranes and also plays an important role in cell signaling events. Cholesterol also acts as a precursor for the biosynthesis of steroids that include sex hormones, glucocorticoids, mineralcorticoids, as well as bile acids and oxysterols. Cholesterol transport is therefore crucial for a host of different physiological processes. The following chapter addresses the involvement and importance of ABC transporters in these different processes. The critical role that ABC transporters play for a successful pregnancy outcome is highlighted by pathological processes that result from
9.1 Introduction .......................................................................................................................... 130 9.2 Placenta and Trophoblast ...................................................................................................... 130 9.3 Cholesterol Transporters ....................................................................................................... 131
9.3.1 ABC Transporter A1................................................................................................. 131 9.3.2 ABC Transporter G1 ................................................................................................. 134
9.4 Cellular Pathways Associated with Cholesterol Transport ................................................... 135 9.4.1 ABCA1 and JAK/STAT Signaling ........................................................................... 135 9.4.2 Effects on Ca2+ Signaling ......................................................................................... 135 9.4.3 Effects on Angiogenesis and Endothelial Dysfunction ............................................ 136 9.4.4 Cholesterol Efux Protects Trophoblasts from Oxysterol-Induced Toxicity ........... 136 9.4.5 Effects on Sonic Hedgehog Pathway ........................................................................ 137
9.5 Pathophysiological Processes Associated with Malfunction of Cholesterol Transport ....... 137 9.6 Avenues of Further Research ................................................................................................ 139
9.6.1 Methods to Study Transplacental Cholesterol Transport ......................................... 139 9.6.2 Dual Placental Perfusion Technique ......................................................................... 139 9.6.3 Transwell® System Using Primary Trophoblast Cells .............................................. 139
Acknowledgments .......................................................................................................................... 141 References ...................................................................................................................................... 142
malfunction of cholesterol transport during pregnancy. Avenues of future research are also described, which may help to further delineate the function and mechanism of action of ABC transporters.
