Abstract
Syncytiotrophoblasts, which form a continuous barrier between the maternal and fetal circulation, play an essential role in restriction of drug delivery through the blood-placental barrier (BPB). In the BPB many influx and efflux transporters for substrates such as neurotransmitters, neuroactive steroids, and nucleosides may play in the development of the fetus and fetal brain. However, the functions of these transporters in BPB, and the molecular and cellular aspects of these transporters remain unclear. The human term placenta and human chorionic carcinoma cell lines, such as BeWo and JAR cells have been mainly used for analysis of transporter and hormone secretion in the placenta. However it is difficult to confirm in vivo evidence using these conventional cell lines. In order to investigate the relationship between in vitro and in vivo results, cell lines from animals as an in vitro model are needed. We have established new syncytiotrophoblast cell lines (TR-TBTs) from the recently developed transgenic rat harboring temperature-sensitive simian virus 40 large T-antigen gene (Tg-rat). TR-TBTs have temperature-sensitive cell growth due to the expression of is SV 40 large T-antigen. These cell lines had a syncytium-like morphology, could be prepared as monolayers, expressed cytokeratins, rat syncytiotrophoblast markers, and in vivo influx and efflux transporters such as oatp2, TauT, GAT-2/BGT-1, and mdr 1 a. Moreover, TR-TBTs exhibited apical or basal GLUT1. localizations and apical GLUT3 localizations. Thus, these results suggest that TR-TBTs could be very useful tool to clarify the BPB functions, including transporter genes and their regulation systems.
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