Mechanotransduction mechanisms for coordinating uterine contractions in human labor

Abstract

This review presents evolving concepts of how the human uterus contracts in pregnancy, with emphasis on the mechanisms of long-distance signaling. Action potential propagation has historically been assumed to be the sole mechanism for signaling and tissue recruitment over both short and long distances. However, data in animals and humans indicate that a single action potential does not travel distances greater than a few centimeters. To address this enigma, a long-distance signaling mechanism based on hydraulic signaling and mechanotransduction is developed. By combining this mechanism for long-distance signaling with the action potential propagation mechanism for signaling over short distances, a comprehensive dual mechanism model (or 'dual model') of uterine function is formulated. Mechanotransduction is an accepted phenomenon of myometrium, but the dual model identifies mechanotransduction as relevant to normal labor. For hydraulic signaling, a local contraction slightly increases intrauterine pressure, which globally increases wall tension. Increased wall tension then mechanically induces additional local contractions that further raise pressure. This leads to robust, positive feedback recruitment that explains the emergence of consistently strong contractions of human labor. Three key components of the dual model - rapid long-distance signaling, mechanical triggering, and electrical activity - converge with the concept of mechanically sensitive electrogenic pacemakers distributed throughout the wall. The dual model retains excitation-contraction coupling and action potential propagation for signaling over short distances (<10cm) and hence is an extension of the action potential model rather than a replacement.