Cholesterol and oxysterol transport in human placental trophoblasts: implications for placental cell viability, differentiation and inflammation

[Truncated abstract] Cholesterol is an essential nutrient which plays a vital role in fetal development. Early in pregnancy, fetal cholesterol levels rise in concert with maternal cholesterol. However, by around 12 and 20 weeks of gestation, changes in fetal cholesterol no longer reflect maternal cholesterol levels, indicating that fetal and maternal cholesterol levels are differentially regulated. As the interface between maternal and fetal circulations, it is hypothesised that the placenta plays an integral role in the regulation of maternal-fetal cholesterol transport. However, the transport mechanisms involved in placental cholesterol transport are poorly understood. ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 are found on the plasma membranes of cells where they mediate the efflux of cholesterol and other sterols. These proteins are expressed ubiquitously, and are responsible for preventing the cellular accumulation of sterols. Through their cholesterol efflux function, ABCA1 and ABCG1 participate, in vivo, in a process known as reverse cholesterol transport, whereby cholesterol from non-hepatic peripheral tissues is trafficked to the liver via the blood stream for elimination. While both of these transporters are expressed highly in the placenta, their function in this organ remains unknown. I hypothesised that placental ABCA1 and ABCG1 play a role in the maternal-fetal cholesterol transport pathway.