Mcnair, R. | Search bioRxiv

bioRxiv2026

Physics-informed stereology for estimating placental diffusive exchange capacity

IntroductionStereological estimates of villous membrane thickness and surface area are widely used to infer the diffusive exchange capacity of the human placenta. A key geometric determinant of exchange capacity can be expressed as an effective diffusive length scale. Here we combine virtual histological sections with computational modelling in realistic villous geometries to assess the accuracy of classical stereological estimates of this diffusive length scale. MethodsTwo terminal villi, reconstructed from three-dimensional imaging, were digitally sectioned to generate random two-dimensional geometries containing fetal capillaries and surrounding villous tissue. For each section, we simulated steady diffusive transport between the fetal-capillary and intervillous-space boundaries to obtain a physics-based diffusive length scale as a reference case. Using the same geometries, we applied standard line-intercept stereology to measure harmonic-mean barrier thickness and boundary-length densities, from which a stereological estimate of diffusive length scale was derived. ResultsAcross both villi, stereology systematically overestimated the diffusive length scale by approximately 15-25%, depending on villus and section. We identified sources of this discrepancy, including interface curvature and assumptions underpinning the stereological correction factors, using idealised models of villous structure. ConclusionThese findings highlight the need for stereological approaches that account for curvature when interpreting placental structure-function relationships.

biophysics↗

bioRxiv2026

The impact of placental structure on haemodynamics and fetal oxygen uptake

The placenta is a fundamental organ for human reproduction, facilitating fetal growth via the exchange of oxygen, nutrients and waste products between mother and fetus, by means of a dense network of fetal villi bathed in maternal blood that flows through the intervillous space (IVS). However, despite its role in adverse pregnancy outcomes associated with impaired maternal-fetal transfer, the influence of placental structure on maternal haemodynamics and the delivery of oxygen and nutrients to the developing fetus is not well understood. This study employs computational fluid dynamics within physiologically informed 2D and 3D whole-organ-scale placental geometries, whose features are informed by recent ex vivo experimental and {micro}CT data, to examine comprehensively the influence of placental anatomy on maternal flow and transport in the IVS. In particular, we consider in detail the impact of the number and placement of maternal decidual arteries and veins that supply and drain the IVS, the location and height of so-called septal walls that loosely separate the placenta into functional units (cotyledons) and sub-units (lobules), and the density of the fetal villous trees as reflected in the rate of uptake of dissolved solutes from the maternal blood and the resistance to flow. We first exploit the computational efficiency of simulation in a representative 2D geometry to study in detail the sensitivity of haemodynamic markers to these parameters. These results guide our 3D study which reveals that the flow, transport and oxygen uptake are strongly influenced by placental structure, and exposes the vein-to-artery ratio as a key indicator of placental efficiency, regulating a trade-off between a preferential maternal flow environment and fetal oxygen uptake. Conversely, the location and height of the septal walls, a feature that is not well studied, have minimal systematic impact on the macroscopic haemodynamic and transport measures considered here. We also introduce a reduced model, for which analytical progress can be made, and demonstrate its utility in exposing key drivers of maternal-fetal transport. Author summaryIn our study, we explored how placental structure affects maternal blood flow and the delivery of oxygen to the fetus. The placenta is a complex and vital organ, but we do not fully understand how its morphology influences its functional efficiency. This is a critical gap in our knowledge as placental blood flow is implicated in serious pregnancy complications such as fetal growth restriction and pre-eclampsia. To investigate the effect of structure, we used detailed 2D and 3D models of the placenta. These models allowed us to simulate maternal blood flow and oxygen transport therein while changing various structural features, such as the number and location of placental veins and the density of the intervillous space. We found that the ratio of veins to arteries is a key factor in determining the maternal blood flow speed and the amount of oxygen the fetus receives. A higher number of veins relative to arteries helps create the slow-flow environment necessary for a healthy pregnancy, but an excessive ratio can reduce the efficiency of oxygen uptake. Our findings suggest that the vein-to-artery ratio could be an important indicator of placental health, offering a new perspective for understanding and enabling effective early intervention treatments of pregnancy complications.

physiology↗