Multiscale computational modeling to quantify how spiral artery remodeling alters wall shear stress on placental villi
- 1Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America
Abstract
Proper placental development is essential for a healthy pregnancy. It depends on the remodeling of the maternal uterine vasculature to meet fetal demands while maintaining physiological intervillous space (IVS) hemodynamics for biochemical exchange. Terminal villi, the primary sites of feto-maternal exchange, exhibit impaired development in pregnancies complicated by intrauterine growth restriction and preeclampsia, which are also associated with incomplete spiral artery (SA) remodeling. Despite this association, the mechanistic link between maternal blood flow and villous development remains unclear. Here, we investigate whether incomplete SA remodeling alters IVS hemodynamics and increases wall shear stress (WSS) on placental villi, potentially impairing terminal villi formation. Computing WSS throughout an entire placentone is challenging due to uncertainty in placental microstructure and the computational cost of resolving microscale hemodynamics. We propose a novel multiscale computational framework to quantify WSS on placental villi at the end of the second trimester, when WSS may affect terminal villi development. A macroscale placentone model is used to compute IVS velocities, which are coupled with microscale models of intermediate villi to estimate villous WSS across physiologically relevant flow conditions. We simulate IVS hemodynamics in healthy pregnancy and varying degrees of incomplete SA remodeling. Our results show that IVS velocity is the primary determinant of mean villous WSS, whereas villous type and orientation have comparatively weaker effects. In healthy placentones, most villi experience a mean WSS of 0.001–1 Pa, with higher stresses localized near the free-of-villi cavity. By correlating these estimates with regions naturally devoid of terminal villi, we identify a mean WSS range of approximately 0.71–1.44 Pa that may inhibit terminal villi formation. Incomplete SA remodeling significantly increases WSS, reaching levels consistent with villous tissue loss and placental lake formation. These findings suggest a mechanistic link between uteroplacental hemodynamics and villi development, establishing physiological shear-stress thresholds relevant to placental health. Author summary: Mechanical forces play an essential role in regulating cell behavior by influencing mechanosensory pathways and biochemical signaling. Although biological processes are often studied from a biochemical perspective, mechanical cues can strongly shape tissue development. This is particularly relevant for the placenta, a growing organ whose proper development is essential for a healthy pregnancy. Placental villi are small, tree-like structures that contain fetal blood vessels and facilitate the exchange of oxygen and nutrients between mother and fetus; their impaired development is commonly observed in complicated pregnancies. In many such pregnancies, the maternal spiral arteries that supply blood to the placenta are only partially remodeled. This incomplete remodeling alters placental blood flow and changes the mechanical forces acting on placental villi. In this study, we developed a computational framework to quantify wall shear stress acting on placental villi under healthy and pathological conditions in a computationally efficient manner. Using this approach, we identified a range of shear stress levels that may hinder terminal villi formation. These findings provide new insight into how altered blood flow mechanics may contribute to abnormal placental development and inform future experimental studies on trophoblast mechanobiology.
Related
- Towards a ML-powered Multiscale Computational Platform Based on QSP and PBPK Modeling to Support the Development of mRNA-based Therapies
- Multiscale Computational Prioritization of Chromone-Based Acetylcholinesterase Ligands
- Disease-associated myeloid states in cardiac remodeling: A new era of cardiac inflammation research enabled by computational biology.
- Computational Modeling of the Acoustic Radiation Force and Viscoelastic Displacement for Transcranial Focused Ultrasound Neuromodulation
- Deficient Monetary Reward Processing in Schizophrenia: A Meta-Analysis and Computational Modeling of a Monetary Incentive Delay Task
BibTeX
@article{najmi2026multiscale,
title = {{Multiscale computational modeling to quantify how spiral artery remodeling alters wall shear stress on placental villi}},
author = {Armita Najmi and Noelia Grande Gutiérrez},
journal = {PLOS Computational Biology},
year = {2026},
month = sep,
doi = {10.1371/journal.pcbi.1014769},
url = {https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014769},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multiscale computational modeling to quantify how spiral artery remodeling alters wall shear stress on placental villi
AU - Armita Najmi
AU - Noelia Grande Gutiérrez
PY - 2026
DA - 2026/09/16
JO - PLOS Computational Biology
DO - 10.1371/journal.pcbi.1014769
UR - https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014769
AB - Proper placental development is essential for a healthy pregnancy. It depends on the remodeling of the maternal uterine vasculature to meet fetal demands while maintaining physiological intervillous space (IVS) hemodynamics for biochemical exchange. Terminal villi, the primary sites of feto-maternal exchange, exhibit impaired development in pregnancies complicated by intrauterine growth restriction and preeclampsia, which are also associated with incomplete spiral artery (SA) remodeling. Despite this association, the mechanistic link between maternal blood flow and villous development remains unclear. Here, we investigate whether incomplete SA remodeling alters IVS hemodynamics and increases wall shear stress (WSS) on placental villi, potentially impairing terminal villi formation. Computing WSS throughout an entire placentone is challenging due to uncertainty in placental microstructure and the computational cost of resolving microscale hemodynamics. We propose a novel multiscale computational framework to quantify WSS on placental villi at the end of the second trimester, when WSS may affect terminal villi development. A macroscale placentone model is used to compute IVS velocities, which are coupled with microscale models of intermediate villi to estimate villous WSS across physiologically relevant flow conditions. We simulate IVS hemodynamics in healthy pregnancy and varying degrees of incomplete SA remodeling. Our results show that IVS velocity is the primary determinant of mean villous WSS, whereas villous type and orientation have comparatively weaker effects. In healthy placentones, most villi experience a mean WSS of 0.001–1 Pa, with higher stresses localized near the free-of-villi cavity. By correlating these estimates with regions naturally devoid of terminal villi, we identify a mean WSS range of approximately 0.71–1.44 Pa that may inhibit terminal villi formation. Incomplete SA remodeling significantly increases WSS, reaching levels consistent with villous tissue loss and placental lake formation. These findings suggest a mechanistic link between uteroplacental hemodynamics and villi development, establishing physiological shear-stress thresholds relevant to placental health. Author summary: Mechanical forces play an essential role in regulating cell behavior by influencing mechanosensory pathways and biochemical signaling. Although biological processes are often studied from a biochemical perspective, mechanical cues can strongly shape tissue development. This is particularly relevant for the placenta, a growing organ whose proper development is essential for a healthy pregnancy. Placental villi are small, tree-like structures that contain fetal blood vessels and facilitate the exchange of oxygen and nutrients between mother and fetus; their impaired development is commonly observed in complicated pregnancies. In many such pregnancies, the maternal spiral arteries that supply blood to the placenta are only partially remodeled. This incomplete remodeling alters placental blood flow and changes the mechanical forces acting on placental villi. In this study, we developed a computational framework to quantify wall shear stress acting on placental villi under healthy and pathological conditions in a computationally efficient manner. Using this approach, we identified a range of shear stress levels that may hinder terminal villi formation. These findings provide new insight into how altered blood flow mechanics may contribute to abnormal placental development and inform future experimental studies on trophoblast mechanobiology.
SN - 1553-7358
ER -