<i>In vitro</i> myometrial contractility reflects indication for caesarean section

Quenby, Siobhán; Matthew, A; Zhang, J.; Dawood, Feroza; Wray, Susan

doi:10.1111/j.1471-0528.2011.03064.x

Cited by 8 publications

(4 citation statements)

References 23 publications

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“…Previous work from our group has shown that in vitro myometrial contractility can reflect in vivo clinical activity and labour outcome [10], [11]. The question therefore arises whether in vitro activity of myometrium from twins is different to that of singletons, making it a useful model for mechanistic studies focussed on risk of preterm labour.…”

Section: Introductionmentioning

confidence: 99%

A Comparison of the Contractile Properties of Myometrium from Singleton and Twin Pregnancies

et al. 2013

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ObjectiveOver half of twin pregnancies in US and UK deliver prematurely but the reasons for this are unclear. The contractility of myometrium from twin pregnancies has not been directly investigated. The objective of this research was to determine if there are differences in the contractile activity and response to oxytocin, between myometrium from singleton and twin pregnancies, across a range of gestational ages. Furthermore, we wished to determine if contractile activity correlates with increasing level of stretch, using neonatal birth weights as a marker of uterine stretch.MethodsThis was an in vitro, laboratory based study of myometrial contractility in women pregnant with one or two babies, using biopsies obtained from non-labouring women undergoing Caesarean section. Spontaneous, oxytocin-stimulated and depolarization induced contractile activity was compared.ResultsDirect measurements of myometrial contractility under controlled conditions show that the frequency of contractions and responses to oxytocin are significantly increased in twins compared to singletons. The duration of contraction however was significantly reduced. We find that contractile activity correlates with increasing levels of stretch, using neonatal birth weights as a surrogate for uterine stretch, with response to oxytocin being significantly positively correlated with birth weight.ConclusionsWe have found significant differences in contractile properties between myometrium from singleton and twin pregnancies and that increasing uterine stretch can alter the contractile properties of myometrium. We discuss the implication of these findings to preterm delivery and future studies.

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Section: Introductionmentioning

confidence: 99%

A Comparison of the Contractile Properties of Myometrium from Singleton and Twin Pregnancies

et al. 2013

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“…11 One reason for insufficient progression of labor is weak contractility of the uterus. 12,13 Low uterine contractility can also delay the initiation of labor, 14 another risky situation for the mother and fetus. 15 Insufficient uterine contractility can also cause postpartum hemorrhage, 16 the leading cause of maternal death.…”

Section: Introductionmentioning

confidence: 99%

Tools, techniques, and future opportunities for characterizing the mechanobiology of uterine myometrium

Maxey

McCain

2021

Exp Biol Med (Maywood)

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The myometrium is the smooth muscle layer of the uterus that generates the contractions that drive processes such as menstruation and childbirth. Aberrant contractions of the myometrium can result in preterm birth, insufficient progression of labor, or other difficulties that can lead to maternal or fetal complications or even death. To investigate the underlying mechanisms of these conditions, the most common model systems have conventionally been animal models and human tissue strips, which have limitations mostly related to relevance and scalability, respectively. Myometrial smooth muscle cells have also been isolated from patient biopsies and cultured in vitro as a more controlled experimental system. However, in vitro approaches have focused primarily on measuring the effects of biochemical stimuli and neglected biomechanical stimuli, despite the extensive evidence indicating that remodeling of tissue rigidity or excessive strain is associated with uterine disorders. In this review, we first describe the existing approaches for modeling human myometrium with animal models and human tissue strips and compare their advantages and disadvantages. Next, we introduce existing in vitro techniques and assays for assessing contractility and summarize their applications in elucidating the role of biochemical or biomechanical stimuli on human myometrium. Finally, we conclude by proposing the translation of “organ on chip” approaches to myometrial smooth muscle cells as new paradigms for establishing their fundamental mechanobiology and to serve as next-generation platforms for drug development.

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“…Other lead compounds currently under development with this assay include retosiban (GSK221149A)38 and nolasiban (data unpublished). These methods have also been used successfully to compare between patient groups39,40,41,42,43,44,45,46,47 and examine for intra-species differences.…”

Section: Introductionmentioning

confidence: 99%

Contractility Measurements of Human Uterine Smooth Muscle to Aid Drug Development

Arrowsmith

Keov

Muttenthaler

et al. 2018

JoVE

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Discovery and characterization of novel pharmaceutical compounds or biochemical probes rely on robust and physiologically relevant assay systems. We describe methods to measure ex vivo myometrium contractility. This assay can be used to investigate factors and molecules involved in the modulation of myometrial contraction and to determine their excitatory or inhibitory actions, and hence their therapeutic potential in vivo. Biopsies are obtained from women undergoing cesarean section delivery with informed consent. Fine strips of myometrium are dissected, clipped and attached to a force transducer within 1 mL organ baths superfused with physiological saline solution at 37 °C. Strips develop spontaneous contractions within 2-3 h under set tension and remain stable for many hours (>6 h). Strips can also be stimulated to contract such as by the endogenous hormones, oxytocin and vasopressin, which cause concentration-dependent modulation of contraction frequency, force and duration, to more closely resemble contractions in labor. Hence, the effect of known and novel drug leads can be tested on spontaneous and agonist-induced contractions.This protocol specifically details how this assay can be used to determine the potency of known and novel agents by measuring their effects on various parameters of human myometrial contraction. We use the oxytocin-and V 1a receptor antagonists, atosiban and SR49059 as examples of known compounds which inhibit oxytocin-and vasopressin-induced contractions, and demonstrate how this method can be used to complement and validate pharmacological data obtained from cell-based assays to aid drug development. The effects of novel agonists in comparison to oxytocin and vasopressin can also be characterized. Whilst we use the example of the oxytocin/ vasopressin system, this method can also be used to study other receptors and ion channels that play a role in uterine contraction and relaxation to advance the understanding of human uterine physiology and pathophysiology.

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In vitro myometrial contractility reflects indication for caesarean section

Abstract: These findings suggest that the myometrium contracts with greater force in women who have a caesarean section for fetal distress.

Cited by 8 publications

References 23 publications

A Comparison of the Contractile Properties of Myometrium from Singleton and Twin Pregnancies

A Comparison of the Contractile Properties of Myometrium from Singleton and Twin Pregnancies

Tools, techniques, and future opportunities for characterizing the mechanobiology of uterine myometrium

Contractility Measurements of Human Uterine Smooth Muscle to Aid Drug Development

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