Paracellular permeability pathways in the human placenta: A quantitative and morphological study of maternal-fetal transfer of horseradish peroxidase

Physiological data indicate that both a transcellular and a paracellular pathway are available for transfer across the human placenta but the morphological correlate of the latter is uncertain. We measured the permeability of the dually perfused human placental cotyledon to the predominantly cationic protein horseradish peroxidase (MW 40,000), to the neutral polymer 14C-dextran (MW 50-70,000) and to the extracellular space marker creatinine (MW 113). Following fixation and cytochemistry, we used brightfield microscopy to localize peroxidase reaction product within the same tissue. Steady state unidirectional maternofetal clearance (K(mf)) for the peroxidase (0.90 ± 0.27 μl/min/g, n = 9) was not significantly different from that for 14C-dextran (0.95 ± 0.07 μl/min/g, n = 3) suggesting that charge does not markedly influence peroxidase permeability. The K(mf) for creatinine was 13.1 ± 2.5 μl/min/g (n = 9); these permeability data are similar to those reported for the placenta in vivo. Microscopically, peroxidase reaction product was localized to the microvillous surface of the syncytiotrophoblast of most villi and to the trophoblastic basement membrane and connective tissue cells of the villous core in a few villi. The reaction product was also associated with fibrin-containing deposits attached to the villous core at sites of discontinuity of the syncytial epithelium. The staining pattern within the deposits was consistent with a diffusion gradient of the peroxidase. These fibrin-containing deposits at discontinuities in the syncytiotrophoblast may provide one paracellular route for peroxidase diffusion from the intervillous space into the villous core.