Why the heart is like an orchestra and the uterus is like a soccer crowd

Smith, Roger; Imtiaz, Mohammad; Banney, David; Paul, Jay P.; Young, Roger C.

doi:10.1016/j.ajog.2015.06.040

Cited by 50 publications

(27 citation statements)

References 38 publications

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“…In these simulations, mathematical models describe the interactions in heterogeneous populations of active and nonactive cells. By varying the degree of coupling and the composition of the populations, various types of patterns of propagations could be mimicked, ranging from clusters, to local, and to global synchronization (1,32,36,37), including the appearance of ectopic and re-entrant or spiral activities (29). Such models could also explain the various types of local, circular, or major contractions described in this study in the guinea pig uterus and suggest that the structure of the tissue, in concert with the topographical expression of functional gap junctions, can determine the origin and pathway of excitation.…”

Section: Discussionmentioning

confidence: 99%

The location of pacemakers in the uteri of pregnant guinea pigs and rats

Lammers

Stephen

Al-Sultan

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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The pregnant uterus is a smooth muscle organ whose pattern of contraction is dictated by the propagation of electrical impulses. Such electrical activity may originate from one or more pacemakers, but the location of these sites has not yet been determined. To detect the location of the pacemaker in the gravid uterus, two approaches were used: 1) determine the site from where the contraction started using isolated uteri from the pregnant guinea pig, and videotape their contractions; and 2) record, in isolated uteri from pregnant term rats, with 240 extracellular electrodes simultaneously, and determine where the electrical bursts started. In both the contractile and electrophysiological experiments, there was not a single, specific pacemaker area. However, most contractions (guinea pig 87%) and bursts (rat 76%) started close to the mesometrial border (mean 2.7 ± 4.0 mm SD in guinea pigs and 1.3 ± 1.4 mm in rats). In addition, in the rat, most sites of initiations were located closer to the ovarial end of the horn (mean distance from the ovarial end 6.0 ± 6.2 mm SD), whereas such an orientation was not seen in the guinea pig. In both guinea pig and rat uteri at term, there is not one specific pacemaker area. Rather, contractile and electrical activity may arise from any site, with the majority starting close to the mesometrial border. Furthermore, in the rat, most activities started at the ovarial end of the horn. This may suggest a slightly different pattern of contraction in both species.

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Section: Discussionmentioning

confidence: 99%

The location of pacemakers in the uteri of pregnant guinea pigs and rats

Lammers

Stephen

Al-Sultan

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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“…At the end of pregnancy, under the drive from the exponential increase of CRH, E 3 concentrations increase more rapidly than concentrations of E 2 , potentially generating E 3 –ER homodimers capable of activating oestrogen‐responsive genes in the myometrium that promote labour. Such labour‐promoting genes activated by oestrogen include gap junction protein alpha 1 ( GJA1 ), which encodes the gap junction protein connexin‐43 that links adjacent myometrial cells, facilitating the development of co‐ordinated contractions (Smith, Imtiaz, Banney, Paul, & Young, ). Oestrogen may also inhibit expression of genes that encode potassium channels (Parkington et al., ), increasing myometrial cell excitability (Tong, Tribe, Smith, & Taggart, ), in addition to affecting expression of progesterone receptor (PR) isoforms (Mesiano et al., ).…”

Section: Corticotrophin‐releasing Hormonementioning

confidence: 99%

“…The unliganded PR‐A then dimerises and translocates to the nucleus, where it interacts with jun/fos heterodimers and promotes GJA1 transcription to produce connexin‐43 and promote labour (Nadeem, Shynlova, Mesiano, & Lye, ). There is also evidence that the unliganded PR‐A isoform is able to promote translation of connexin‐43 and movement of the connexin protein to the surface of myocytes to facilitate formation of connexin junctions with neighbouring cells, facilitating the development of the synchronised contractile behaviour required to increase intrauterine pressure (Smith et al., ). The myometrium therefore tips from a relaxed to a contractile phenotype though a change in PR isoforms.…”

Section: Progesteronementioning

confidence: 99%

Sharpey‐Schafer Lecture 2019: From retroviruses to human birth

Smith

Paul

Tolosa

2020

Experimental Physiology

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Gestational length at the time of birth is an important determinant of future health and well-being, yet the physiological regulation of the onset of labour in humans remains obscure. The evolution of egg formation and internal fertilisation in amniotes required a mechanism to suppress the contractile activity of the oviduct that is provided by progesterone. Delivery of the egg is then associated with the withdrawal of progesterone and a return of contractile activity to the reproductive tract.In mammals, the process of pregnancy is complicated further by the need to protect the fetus from potential attack by the maternal immune system. There is increasing evidence that retroviruses incorporated into the mammalian germline in the evolutionary past play a key role in suppressing the maternal immune reaction to the developing conceptus, organising the development of the placenta and perhaps, in humans, modulating the action of progesterone, determining gestational length and the onset of labour. It seems that the presence of an endogenous retrovirus is an obligate requirement for human reproduction.

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“…We appreciate the letter of Dr Andersen, and we wholeheartedly acknowledge the contributions of Mel Barclay for not only his scientific work but also as the true humanist he was. However, there are important differences between the physiological assumptions of organ-level contractility that we used and those used by Andersen and Barclay in 1995 1 and Barclay, Andersen, and Simon in 2010. 2 In both papers, the authors assumed the presence of a small number of functional pacemakers (perhaps only one, though) and that the only means of recruiting new tissue into each contraction is through direct cell-to-cell signaling as the action potential passes through tissue.…”

Section: Replymentioning

confidence: 99%

Why the heart is like an orchestra and the uterus is like a soccer crowd

Andersen

2016

American Journal of Obstetrics and Gynecology

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Why the heart is like an orchestra and the uterus is like a soccer crowd TO THE EDITORS: Thank you for your interesting commentary on the mechanism of uterine activity leading to organized labor. 1 Your analogy of the soccer stadium (or perhaps football in an American context) for uterine contractility in labor as compared with the organized sequence of cardiac contractility is very apt. It is almost certainly true that organized uterine contractions (labor) are possible only because of the ability of electrical activity to propagate through gap junctions. Drs Mel Barclay, Carl Simon, and I investigated a computer model of uterine activity based on the concept of propagation via gap junctions. 2 The model demonstrated organized propagation of contractile activity when adequate connections were available between the cells of the computer model. 3 Dr Barclay and I had many conversations about the presence or absence of a pace-making function in the uterus. He believed that the anatomic studies of Toth and Toth 4 demonstrated a pacemaker region, whereas I am skeptical. The computer model, 5 admittedly simple, that we developed required a pacemaker function for prolonged contractile activity; however, we found some evidence that more accurate modeling of electrical characteristics of the cells would generate self-sustaining patterns. I suspect that regions of the myometrium with higher rates of contractility eventually take over the coordination of contraction patterns. Unfortunately, our studies did not continue after Dr Barclay's death in 2010. I continue to believe that further modeling of the uterus as a construction of cellular automata with connections governed by physiological and electrochemical processes that you summarize will advance our understanding of both organized and disorganized (dysfunctional) labor.

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Why the heart is like an orchestra and the uterus is like a soccer crowd

Cited by 50 publications

References 38 publications

The location of pacemakers in the uteri of pregnant guinea pigs and rats

The location of pacemakers in the uteri of pregnant guinea pigs and rats

Sharpey‐Schafer Lecture 2019: From retroviruses to human birth

Why the heart is like an orchestra and the uterus is like a soccer crowd

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