Digital capture of the histological microarchitecture in the myometrium and its implications for the propagation of electrophysiological excitation.

Abstract

Coordination of uterine contractions during labour is critical for successful delivery. The mechanisms underlying this coordination are not fully understood. Propagation of contraction signals has previously been observed to occur through transmission of electrical excitation waves. This thesis aims to examine the histological microarchitecture of the muscular layer of the uterus (myometrium) and determine how this structure affects the propagation of excitation by means of in silico three-dimensional reconstruction of the myometrium and numerical simulations of a spatially structured excitation-relaxation model. A key aim of the in silico reconstruction of the smooth muscle architecture of the myometrium is to identify structural features that correspond to the control of excitation behaviour in the myometrium. This examination is aided by analysis of excitation patterns observed in multi-electrode array recordings. The reconstruction is subsequently used as a basis for simulating electrical activity in the myometrium. Novel structural features are identified here that are located at the initiation points of electrical activity and are proposed to be the pacemaker sites in rat myometrium. Furthermore, boundary of low connectivity across the mesometrial border was observed in the rat, which corresponds to the termination of excitation waves observed in multielectrode array recordings. In addition, bridges of smooth muscle cells connecting the inner and outer layers of the myometrium were observed in both rat and human myometrium. Taken together these three features suggest a novel mechanism for control of contraction in the rat myometrium; an analogous mechanism is proposed for the human myometrium. The results presented in this thesis could provide an explanation for the patterns of excitation propagation observed in human and rat uteri. Further refinements of the methods used here are outlined and expected to generate a more detailed visualisation of the structures underpinning these mechanisms