Except for the brain, the only other organ in the human body that does not have a generally accepted physiological model of function is the laboring uterus. Parturition appears to be regulated by local mechanisms, since input from the central nervous system is lacking. However, the mechanisms that initiate and maintain human labor remain enigmatic. Many key cellular processes and signaling systems have been identified, such as sterile inflammation and signaling from the fetus. However, there remain fundamental knowledge gaps involving signaling between cells, through tissue, and globally across the pregnant uterus. In pioneering work, Caldeyro-Barcia and others proposed that action potential propagation was the dominant, if not sole, mechanism for global uterine communication. Strong evidence subsequently emerged that questioned the validity of this hypothesis, implying that other tissue- and organ-level communication mechanisms function during labor. Many such candidate processes have been identified, but it is unclear which are important in either term or preterm labor.

At the present time, there is no effective intervention that prolongs pregnancy and prevents preterm birth. Prematurity results in significant morbidly that can result in life-long illness. The primary goal is to elucidate the important intercellular signaling mechanisms used by the human uterus, and to identify more precise, and safer, methods to clinically modulate uterine contractions of preterm and term labor. To achieve the primary goal, secondary goals are to identify new signaling mechanisms, or refine established mechanisms, that directly contribute to labor, and to understand the clinical conditions where each mechanism contributes or perhaps dominates. While there is a broad and deep understanding of cellular processes, the focus here is to move beyond mechanisms that are largely contained within cells, and into a further understanding of intercellular processes, including global signaling across the entire uterus.

The scope of this topic encompasses all intercellular signaling mechanisms that may function during human labor. However, it is clear that animal studies can be crucially important, especially in pioneering investigations. The emphasis will be not only on elucidating mechanisms, but on medications and techniques that modulate signaling, and to promote technology that can evaluate signaling in vivo. Manuscripts that address mechanisms necessary and sufficient to produce globally coordinated, strong contractions are of particular interest. Specific systems include (but are not limited to): generation, propagation, and termination of electrical events; mechanotransduction mechanisms; inflammation; paracrine and endocrine signaling; and previously overlooked or underemphasized signaling mechanisms.

Topic Editor Dr. Yong Wang is the inventor and patent holder of a uterine contraction imaging device. Topic Editor Dr. Roger Young is the Chief Medical Officer, founder, and shareholder of PreTeL, Inc Dr. Young is also the holder of the following patents, to which PreTeL holds exclusive rights: [1] RC Young. Predicting and Monitoring Labor. 503826055; WO PCT/US2015/057352. (Issued: May 16, 2016); [2] RC Young. Measuring Bioelectrical Signals of Intra-abdominal Organs. US14/922,955. (Issued: November 13, 2018). Dr. Young also declares that none of the aforementioned create a competing financial interest with the Research Topic project. Topic Editors Dr. Iain Buxton and Dr. Mark Johnson declare no potential competing interests with regard to the Research Topic subject.

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