PT  - JOURNAL ARTICLE
AU  - Rohan M Lewis
AU  - Harikesan Baskaran
AU  - Jools Green
AU  - Stanimir Tashev
AU  - Eleni Paleologou
AU  - Emma M Lofthouse
AU  - Jane K Cleal
AU  - Anton Page
AU  - David S Chatelet
AU  - Patricia Goggin
AU  - Bram G Sengers
TI  - 3D Visualisation of trans-syncytial nanopores provides a pathway for paracellular diffusion across the human placental syncytiotrophoblast
AID  - 10.1101/2022.01.26.477815
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.26.477815
4099  - http://biorxiv.org/content/early/2022/09/02/2022.01.26.477815.short
4100  - http://biorxiv.org/content/early/2022/09/02/2022.01.26.477815.full
AB  - 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 modelling 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.Competing Interest StatementThe authors have declared no competing interest.