3D visualization of trans-syncytial nanopores provides a pathway for paracellular diffusion across the human placental syncytiotrophoblast
Rohan M. Lewis,
Harikesan Baskaran,
Jools Green,
Stanimir Tashev,
Eleni Palaiologou,
Emma M. Lofthouse,
Jane K. Cleal,
Anton Page,
David S. Chatelet,
Patricia Goggin,
Bram G. Sengers
Affiliations
Rohan M. Lewis
Faculty of Medicine, Southampton General Hospital, University of Southampton, MP 887, IDS Building, University Road, Southampton SO17 1BJ, UK; Institute for Life Sciences, University of Southampton, University Road, Southampton SO17 1BJ, UK; Corresponding author
Harikesan Baskaran
Faculty of Engineering and Physical Sciences, University of Southampton, University Road, Southampton SO17 1BJ, UK
Jools Green
Faculty of Medicine, Southampton General Hospital, University of Southampton, MP 887, IDS Building, University Road, Southampton SO17 1BJ, UK
Stanimir Tashev
Faculty of Medicine, Biomedical Imaging Unit, University of Southampton, University Road, Southampton SO17 1BJ, UK
Eleni Palaiologou
Faculty of Medicine, Southampton General Hospital, University of Southampton, MP 887, IDS Building, University Road, Southampton SO17 1BJ, UK
Emma M. Lofthouse
Faculty of Medicine, Southampton General Hospital, University of Southampton, MP 887, IDS Building, University Road, Southampton SO17 1BJ, UK
Jane K. Cleal
Faculty of Medicine, Southampton General Hospital, University of Southampton, MP 887, IDS Building, University Road, Southampton SO17 1BJ, UK; Institute for Life Sciences, University of Southampton, University Road, Southampton SO17 1BJ, UK
Anton Page
Faculty of Medicine, Biomedical Imaging Unit, University of Southampton, University Road, Southampton SO17 1BJ, UK
David S. Chatelet
Faculty of Medicine, Biomedical Imaging Unit, University of Southampton, University Road, Southampton SO17 1BJ, UK
Patricia Goggin
Faculty of Medicine, Biomedical Imaging Unit, University of Southampton, University Road, Southampton SO17 1BJ, UK
Bram G. Sengers
Institute for Life Sciences, University of Southampton, University Road, Southampton SO17 1BJ, UK; Faculty of Engineering and Physical Sciences, University of Southampton, University Road, Southampton SO17 1BJ, UK
Summary: The placental syncytiotrophoblast, a syncytium without cell-cell junctions, is the primary barrier between the mother and the fetus. Despite no apparent anatomical pathway for paracellular diffusion of solutes across the syncytiotrophoblast, size-dependent paracellular diffusion is observed. Here we report data demonstrating that the syncytiotrophoblast is punctuated by trans-syncytial nanopores (TSNs). These membrane-bound TSNs directly connect the maternal and fetal facing sides of the syncytiotrophoblast, providing a pathway for paracellular diffusion between the mother and fetus. Mathematical modeling of TSN permeability based on their 3D geometry suggests that 10–37 million TSNs per cm3 of placental tissue could explain experimentally observed placental paracellular diffusion. TSNs may mediate physiological hydrostatic and osmotic pressure homeostasis between the maternal and fetal circulations but also expose the fetus to pharmaceuticals, environmental pollutants, and nanoparticles.
