The Role and Regulation of the Nuclear Factor Kappa B Signalling Pathway in Human Labour

Abstract Within the discipline of reproductive biology, our understanding of one of the most fundamental biological processes is lacking—the cellular and molecular mechanisms that govern birth. This lack of understanding limits our ability to reduce the incidence of labour complications. The incidence of labour complications including: preterm labour; cervical incompetence; and post-date pregnancies has not diminished in decades. The key to improving the management of human labour and delivery is an understanding of how the multiple processes that are requisite for a successful labour and delivery are coordinated to achieve a timely birth. Processes of human labour include the formation of: contraction associated proteins; inflammatory mediators (e.g. cytokines); uterotonic phospholipid metabolites (e.g. prostaglandins); and the induction of extracellular matrix (ECM) remodelling. Increasingly, it is becoming evident that labour onset and birth are the result of cross-talk between multiple components of an integrated network. This hypothesis is supported by recent data implicating various upstream regulatory pathways in the control of key labour-associated processes, including the activity of enzymes involved in the formation of prostaglandins and extracellular matrix remodelling, and mediators of inflammation. Clearly, the biochemical pathways involved in the formation of these mediators represent potential sites for intervention that may translate to therapeutic interventions to delay or prevent preterm labour and delivery. Available data strongly implicate the nuclear factor-κB (NF-κB) family as candidate upstream regulators of multiple labour-associated processes. Not only do these data warrant further detailed analysis of the involvement of these pathways in the process of human labour but also promise new insights into the key mechanisms that trigger birth and the identification of new therapeutic interventions that will improve the management of labour.