Hussan, J. R.; Means, S. A.; Hunter, P. J.; Clark, A. R.

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 pacemakers. 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 ({approx} 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.