ABSTRACT
It is not surprising that research directed toward pre - term delivery has focused on the onset of labor. Indeed, the vast majority of research investigations relating to myometrial function, including our own, have focused on events during the last few hours of pregnancy. Over the past decade our knowledge of the mechanisms leading to the onset of labor has increased dramatically (see ref 3 for detailed review). We have proposed that the fetal genome ultimately regulates the timing of parturition, and that this is accomplished through two separate but integrated pathways; an endocrine cascade comprising the fetal hypothalamic-pituitary-adrenalplacental axis, and a mechanical pathway in which fetal growth imposes tension of the uterine wall inducing biochemical and molecular changes within
the myometrium. Both of these pathways are required in order to increase the expression of a cassette of contraction-associated proteins (CAP; e.g. the gap junction protein Cx43, receptors for agonists such as oxytocin and stimulatory prostaglandins, and Na/Ca ion channels that control myometrial excitability) that induce activation of the myometrium. We now believe that these signals modulate the expression of a much wider cadre of genes including extracellular matrix (ECM) proteins, cell-matrix adhesion complexes5 and contractile proteins,6 and thus control the contractile phenotype of uterine myocytes at labor. Once activated, the myometrium can optimally respond to the increased production of uterine agonists (e.g. oxytocin, stimulatory prostaglandins), which in turn drive myometrial contractions required for delivery of the fetus.
