We present a hypothesis for a mechanism involving self-organization of small functional units that leads to organ-level synchronization of uterine contractions in human labor. This view is in contrast to the long-held presumption that the synchronized behavior of the uterus is subject to well-defined internal organization (as is found in the heart) that exists prior to the onset of labor. The contractile units of the uterus are myocytes, which contract in response to both mechanical stretch and electrical stimulation. Throughout pregnancy progesterone maintains quiescence by suppression of "contraction-associated proteins" (CAPs). At the end of pregnancy a functional withdrawal of progesterone and an increasingly estrogenic environment leads to an increase in the production of CAPs. One CAP of particular importance is connexin 43, which creates gap junctions between the myocytes that cause them to become electrically coupled. The electrical connectivity between myocytes, combined with an increase in intrauterine pressure at the end of pregnancy shifts the uterus towards an increasingly unstable critical point, characterized by irregular, uncoordinated contractions. We propose that synchronous, coordinated contractions
OPEN ACCESSSymmetry 2015, 7 1982 emerge from this critical point through a process of self-organization, and that the search for a uterine pacemaker has been unfruitful for the sole reason that it is non-existent.
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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