The Myometrium: From Excitation to Contractions and Labour

Wray, Susan; Prendergast, Clodagh

doi:10.1007/978-981-13-5895-1_10

Cited by 56 publications

(64 citation statements)

References 187 publications

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“…Over the course of gestation, the myometrium transitions from a state of quiescence during pregnancy to one of contractile activity during labor in response to both hormonal and mechanical signals. Concomitant changes in gene expression that accompany this transition are thought to be a driving force for the initiation of labor [1,2]; however, little is known about the molecular mechanisms underlying these changes. Across developmental contexts, the chromatin landscape is thought to maintain a cell's identity.…”

Section: Introductionmentioning

confidence: 99%

The pregnant myometrium is epigenetically activated at contractility-driving gene loci prior to the onset of labor in mice

et al. 2020

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During gestation, uterine smooth muscle cells transition from a state of quiescence to one of contractility, but the molecular mechanisms underlying this transition at a genomic level are not well-known. To better understand these events, we evaluated the epigenetic landscape of the mouse myometrium during the pregnant, laboring, and postpartum stages. We generated gestational time point-specific enrichment profiles for histone H3 acetylation on lysine residue 27 (H3K27ac), histone H3 trimethylation of lysine residue 4 (H3K4me3), and RNA polymerase II (RNAPII) occupancy by chromatin immunoprecipitation with massively parallel sequencing (ChIP-seq), as well as gene expression profiles by total RNA-sequencing (RNA-seq). Our findings reveal that 533 genes, including known contractility-driving genes (Gap junction alpha 1 [Gja1], FBJ osteosarcoma oncogene [Fos], Fos-like antigen 2 [Fosl2], Oxytocin receptor [Oxtr], and Prostaglandin G/H synthase 2 (Ptgs2), for example), are upregulated at day 19 during active labor because of an increase in transcription at gene bodies. Labor-associated promoters and putative intergenic enhancers, however, are epigenetically activated as early as day 15, by which point the majority of genome-wide H3K27ac or H3K4me3 peaks present in term laboring tissue is already established. Despite this early exhibited histone signature, increased noncoding enhancer RNA (eRNA) production at putative intergenic enhancers and recruitment of RNAPII to the gene bodies of labor-associated loci were detected only during labor. Our findings indicate that epigenetic activation of the myometrial genome precedes active labor by at least 4 days in the mouse model, suggesting that the myometrium is poised for rapid activation of contraction-associated genes in order to exit the state of quiescence.

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Section: Introductionmentioning

confidence: 99%

The pregnant myometrium is epigenetically activated at contractility-driving gene loci prior to the onset of labor in mice

et al. 2020

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“…Still, treatment with the RyR inhibitor ryanodine had little effect on mouse, rat or human myometrium 28,34,35 . Thus, RyRs are likely not important contributors to SR calcium release in mouse, rat, guinea pig or human 36 …”

Section: Physiology Of Uterine Contractionsmentioning

confidence: 97%

“…28,34,35 Thus, RyRs are likely not important contributors to SR calcium release in mouse, rat, guinea pig or human. 36 Both intracellular and extracellular Ca 2+ sources help regulate myometrial contractility via the process of store-operated calcium entry (SOCE). When the SR releases Ca 2+ through the IP 3 receptor, Ca 2+ concentration in the SR lumen drops, leading to a conformational change in the stromal interaction molecule (STIM) protein located on the SR membrane (Figure 2).…”

Section: Mechanism Of Uterine Contractionsmentioning

confidence: 99%

Uterine contractions in rodent models and humans

2021

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Aberrant uterine contractions can lead to preterm birth and other labour complications and are a significant cause of maternal morbidity and mortality. To investigate the mechanisms underlying dysfunctional uterine contractions, researchers have used experimentally tractable small animal models. However, biological differences between humans and rodents change how researchers select their animal model and interpret their results. Here, we provide a general review of studies of uterine excitation and contractions in mice, rats, guinea pigs, and humans, in an effort to introduce new researchers to the field and help in the design and interpretation of experiments in rodent models.

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“…However, the results can be affected by obesity, diabetes, gestation, the presence or absence of labour, singleton or twin pregnancy, and fibrosis from previous uterine surgery [32][33][34][35]. Furthermore, data should be interpreted in the context of these biopsies being obtained from a gravid uterus, which has undergone massive hypertrophy [36] and has been exposed to the pregnancy related hormonal milieu [37]. The location of the myometrial biopsy may also have implications for data analysis; for example, a biopsy taken from the upper uterine segment at a classical CS (where a vertical incision is made into the upper uterine segment) may have different properties to the myometrium obtained from a lower uterine segment [38]; however, in relation to contractility studies, current evidence suggests that there is no significant difference between myometrial biopsies obtained from upper and lower uterine segments [39].…”

Section: Harvesting the Myometriummentioning

confidence: 99%

Human Uterine Biopsy: Research Value and Common Pitfalls

Maclean

Kamal

Adishesh

et al. 2020

International Journal of Reproductive Medicine

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The human uterus consists of the inner endometrium, the myometrium, and the outer serosa. Knowledge of the function of the uterus in health and disease is relevant to reproduction, fertility, embryology, gynaecology, endocrinology, and oncology. Research performed on uterine biopsies is essential to further the current understanding of human uterine biology. This brief review explores the value of the uterine biopsy in gynaecological and human fertility research and explores the common problems encountered when analysing data generated from different types of uterine biopsies, with the aim of improving the quality, reproducibility, and clinical translatability of future research.

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The Myometrium: From Excitation to Contractions and Labour

Cited by 56 publications

References 187 publications

The pregnant myometrium is epigenetically activated at contractility-driving gene loci prior to the onset of labor in mice

The pregnant myometrium is epigenetically activated at contractility-driving gene loci prior to the onset of labor in mice

Uterine contractions in rodent models and humans

Human Uterine Biopsy: Research Value and Common Pitfalls

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