MECHANISMS OF PARTURITION
The process of normal spontaneous parturition can be divided into four stages (see the reviews of Challis  and Challis et al. ). During most of pregnancy, the uterus remains relatively quiescent, and this corresponds to Phase 0 (quiescence) of parturition. Phase 1 (activation) involves uterine stretch and fetal hypothalamic-pituitary-adrenal (HPA) activation. Phase 2 (stimulation) refers to stimulation of the activated uterus by various substances, including corticotropin-releasing hormone (CRH), oxytocin, and prostaglandins. These different processes lead to a common pathway to parturition involving increased uterine contractility, cervical ripening, and decidual and fetal membrane activation (Romero et al., 2004a). Phase 3 (involution) corresponds to postpartum involution of the uterus. These unique phases are described below and are summarized in Figure 6-1.
FIGURE 6-1 The stages of parturition. Following implantation, more than 95 percent of gestation is spent in Phase 0, uterine quiescence. During quiescence, myometrial contractility is inhibited by a variety of biological substances, including progesterone. Phase 1, myometrial activation, is characterized by increased expression of contraction-associated proteins, receptors for oxytocin, and prostaglandins, and increased placental estrogen biosynthesis. The signal for myometrial activation is controlled by the fetal HPA axis, which, in turn, is up-regulated by endogenous placental CRH production. Phase 2, myometrial stimulation, involves a progressive cascade of events, beginning with myometrial activation, which results in myometrial contractility, cervical ripening, and decidua and membrane activation. It is likely initiated by the same events of fetal HPA activation that initiate Phase 1. Phase 3, involution, involves placental separation and contraction of the uterus. It is primarily effected by maternal oxytocin. Implantation