Although little evidence suggests a role for oxytocin in phase 2 of parturition, abundant data support its important role during second-stage labor and in the puerperium-phase 4 of parturition. Speciically, maternal serum oxytocin levels are elevated: (1) during second-stage labor, which is the end of phase 3 of parturition; (2) in the early puerperium; and (3) during breastfeeding (Nissen, 1995). Immediately after delivery of the fetus, placenta, and membranes, which completes parturition phase 3, irm and persistent uterine contractions are essential to prevent postpartum hemorrhage. Oxytocin likely causes persistent contractions.
Although their role in phase 2 of parturition in uncomplicated pregnancies is less well defined, a critical role for prostaglandins in phase 3 of parturition is clear (MacDonald, 1993). First, levels of prostaglandins-or their metabolites-in amnionic luid, maternal plasma, and maternal urine are increased during labor. Second, receptors for PGE2 and PGF2x are expressed in the uterus and cervix. Thus, if these tissues are exposed to prostaglandins, they will respond. Third, treatment of pregnant women with prostaglandins, by any of several administration routes, causes abortion or labor at all gestational ages. Moreover, administration of prostaglandin H synthase type 2 (PGHS-2) inhibitors to pregnant women will delay spontaneous labor onset and sometimes arrest preterm labor (Loudon, 2003). Last, prostaglandin treatment of myometrial tissue in vitro sometimes causes contraction, dependent on the prostanoid tested and the physiological status of the tissue treated.
During labor, prostaglandin production within the myometrium and decidua is an eicient mechanism of activating contractions. For example, prostaglandin synthesis is high and unchanging in the decidua during phase 2 and 3 of parturition. Moreover, the receptor level for PGF2x is augmented in the decidua at term, and this increase most likely is the regulatory step in prostaglandin action in the uterus.
he fetal membranes and placenta also produce prostaglandins. Primarily PGE2, but also PGF2x, are detected in amnionic fluid at all gestational ages. As the fetus grows, prostaglandin levels in the amnionic fluid rise gradually. heir greatest
FIGURE 21-18 Sagittal view of the exposed forebag and attached decidual fragments after cervical dilation during labor. (Redrawn from MacDonald PC, Casey ML: Preterm birth. Sci Am 3:42, 1996.) elevation in concentration within amnionic luid, however, is demonstrable after labor begins. hese higher levels likely result as the cervix dilates and exposes decidual tissue (Fig. 21-18). hese higher levels in the forebag, compared with those in the upper compartment, are believed to follow an inflammatory response that signals the events leading to active labor. Together, the rise in cytokine and prostaglandin concentrations further degrade the extracellular matrix, thus weakening fetal membranes.
The endothelins are a family of 21-amino-acid pep tides that powerfully induce myometrial contraction (Word, 1990). The endothelin A receptor is preferentially expressed in smooth muscle, and when activated, it efects a rise in intracellular calcium. Endothelin-1 is produced in myometrium of term gestations and is able to induce synthesis of other contractile mediators such as prostaglandins and inflammatory mediators (Momohara, 2004; Sutclife, 2009). The requirement of endothelin-1 in normal parturition physiology remains to be established.