Septal venous drainage facilitates oxygen-transfer kinetics in the human placenta

<title>Abstract</title> <p>Efficient materno–fetal oxygen transfer depends on continual renewal of oxygen gradients in placental intervillous spaces (lacunae), where fetal capillaries, encased in chorionic villi, float freely in maternal blood. The pathways for maternal venous drainage from these lacunae are poorly defined. Combining structural analysis of term placentae with near-physiological ex vivo dual-perfusion, we identified EphB4⁺ veins within decidual septa as an additional important discrete maternal exit pathway. In normal placentae, with septal veins, umbilical venous oxygen peaked (Pr = 9.8%) within 2.8 min (Tp). In small-for-gestational-age and high-BMI pregnancy groups — with elevated stillbirth risk — septal veins were absent with Tp &gt; 10 min, although peak oxygenation was eventually reached. Multivariate analysis associated septal-vein presence with oxygen-transfer kinetics and fetal growth. Continual renewal of intervillous oxygen gradients, not maximal transfer capacity alone, constrains placental efficiency. Absent septal venous drainage narrows the margin of fetal oxygen reserves, increasing susceptibility to stillbirth.</p>