Michal Meir, Ameer Bishara, Emma Portnoy, Miri Shmuel, Sara Eyal
Institute for drug research, School of Pharmacy, the Hebrew University of Jerusalem, Jerusalem, Israel
Objectives: The transfer of nutrients, xenobiotics and waste compounds between mother and fetus is performed by passive diffusion or by placental transporters. The goal of this project was to develop a near infra-red (NIR) imaging methodology for studying the integrity of the placental barrier and the functional activity of placental transporters.
Methods: The study was conducted in mice on gestational day 17.5 (late-gestation). Indocyanine green (ICG) (8 mg/kg, i.v.), which is a substrate of several placental transporters and normally does not cross the placenta, was used as the NIR probe. Valspodar (12.5 mg/kg, i.p.) was used as a transporter modulator.
Results: Under normal conditions, ICG transfer across the placenta was minimal. Valspodar significantly (3.3-fold and 3.1-fold; P<0.01) increased ICG’s transfer into the fetus and accumulation within the placenta, respectively. The increase in ICG accumulation within the placenta remained significant after normalization by blood ICG, suggesting enhanced ICG transfer from blood across both the apical and the basolateral membrane of the syncytiotrophoblast.
Conclusions: ICG accumulation within the placenta suggests an effect of valspodar on placental permeability, possibly through modulation of placental transporters activity. The results emphasize the role of the placenta as a protective barrier for the fetus. The effects of xenobiotic accumulation and modulation of the placental tissue require further investigation.