Computational physiology of uterine smooth muscle

Abstract

Pregnancy can be accompanied by serious health risks to mother and child, such as pre-eclampsia, premature birth and postpartum haemorrhage. Understanding of the normal physiology of uterine function is essential to an improved management of such risks. Here we focus on the physiology of the smooth muscle fibres which make up the bulk of the uterine wall and which generate the forceful contractions that accompany parturition. We survey computational methods that integrate mathematical modelling with data analysis and thereby aid the discovery of new therapeutic targets that, according to clinical needs, can be manipulated to either stop contractions or cause the uterine wall muscle to become active.

Effect of Aging on the Human Myometrium at Single-Cell Resolution

“…While we did not observe specific age-related changes in the abundance of fibroblasts, we did detect the upregulation of aging-associated genes (FOS, FOSB, and NFATC2) in universal PI16 + and COL15A1 + fibroblasts, classic fibroblasts, and intermediate NRP1+ fibroblasts during myometrial aging. SMCs also exhibited reduced functionality, as shown by the downregulated expression of contractility-associated genes (e.g., ACTG2, MYL6, MYL9, TPM2, or DES) despite an increase in their relative number, which may represent an attempt to compensate for the age-related loss of functionality and reduced contractility 20,32,35 . Stimuli-response SMCs in the aging myometrium downregulated the expression of KCNE4, a type I beta subunit that assembles with the channel complex to modulate the gating kinetics and enhance stability 36 and VDAC2, whose loss has been linked to cardiac muscle atrophy in mice 37 .…”

Development of a portable labor-contraction monitor based on mechanomyography

“…Meanwhile, the myometrium, mainly composed of smooth cells, is expected to initiate a mechanical contraction like that of other muscle tissues. Still, it can present circularly and longitudinally orientated muscle layers highly interwoven with associated characteristics, such as a slow, intense, and prolonged contraction [Dunford et al 2019], presenting a particular state in which the uterine muscle fibers remain shortened after contracting, called retraction.…”