A Computational Functional Tissue Unit of the Human Myometrium for In Silico Study of Gestational Excitability and Pathophysiology

Abstract The human myometrium undergoes a dramatic transformation during pregnancy, shifting from quiescence to highly synchronised contractility. Understanding this transition is crucial for addressing pathologies such as preterm labour and dystocia (ineffective labour). We present a multi-scale Functional Tissue Unit (FTU) model allowing us to investigate how tissue-level excitability emerges from single-cell electrophysiology. We propose a heterogeneity-driven selection mechanism, wherein a sub-population of cells with high intrinsic excitability dynamically emerges as pace-makers. This active process complements passive depolarisation by interstitial cells, allowing spontaneous excitation to arise without a fixed anatomical pacemaker. Stochastic simulations produced an average burst frequency of 0.047 Hz (≈2.8 bursts per minute), closely consistent with clinical measurements of 2–3 contractions per minute during active labour, and demonstrated that this function is robust to spatial topological changes. Furthermore, implementation of inflammation-induced remodelling simulations successfully linked molecular-level changes to a preterm labour phenotype. This model provides a platform for investigating uterine contractility and serves as a component for future whole-organ Physiome models. Competing Interest Statement The authors have declared no competing interest.