Understanding what triggers birth? New opportunities for prevention of early delivery
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 that include the formation of: contraction associated proteins [CAPs]; inflammatory mediators [eg cytokines]; uterotonic phospholipid metabolites [eg prostaglandins]; and the induction of extracellular matrix remodelling.
New approaches that identify and target the upstream regulators of multiple labour-associated processes are required if better management of labour is to be achieved. Over the last decade, my studies have identified a number of “master regulators” of the mechanisms that govern birth. My in vitro data has made it increasingly clear that a suite of regulators (e.g. nuclear factor-κB, NF-κB; peroxisome proliferator activated receptors, PPARs; activator protein, AP-1; sirtuin 1, SIRT1) coordinate the timely expression of the terminal effector pathways of labour and delivery. These master regulators may represent novel intervention points for developing therapeutics to reduce the incidence of preterm birth and related perinatal morbidity and mortality. In this project, we will thoroughly characterise their role in preterm birth and investigate their potential as a therapeutic intervention to prevent preterm labour using a mouse model of preterm birth.
Norman Beischer Medical Research Foundation
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