No other neuroendocrine mechanism is as integrative and dynamic as that of labor and delivery. Fine-tuned coordination of a series of physiological reactions between the fetus, placenta, and mother is imperative for labor to end in successful birth. Problems associated with labor and parturition (dystocia) are not uncommon. The complexity of the multistep labor/parturition process predisposes it to disorder and malfunction - sometimes necessitating a cesarean ("to cut") section.
Stages. Three progressive stages (I, II, and III) define the birth process. Stage I is preparative for delivery; during this time the uterus undergoes rhythmic contractions and ligaments that hold the pelvic bones together relax (Figure 5-34). The connective tissue network of the cervix also is degraded and becomes disorganized (ripening), leading to cervical compliancy (softening), effacement (thinning), and dilation. It is often difficult to diagnose the actual onset of labor. Women should be considered in Stage I labor when uterine contractions occur every two-to-three minutes. Intermittent (Braxton-Hicks) contractions are often mistaken as true labor. Human Stage I is complete when the cervix has dilated to 10 cm.
The fetus is expelled during Stage II labor. The onset of Stage II is marked by rupture of the chorioallantoic membrane and drainage of allantoic fluid (ie., breakage of the first "water bag"). The amnion ruptures as the fetus progresses through the cervical canal. Normal presentation of the fetus is head first (Figure 5-35). Fetal delivery is sometimes complicated when the feet or buttocks (breech) are delivered first. In women the vaginal opening is sometimes enlarged by incising the perineum (episiotomy). The detached placenta is expelled during Stage III labor. Placenta previa is a condition in which the placenta obstructs the cervical canal and normal fetal delivery.
A model. Much of what has been learned about labor and parturition has come from experiments with sheep; I will consider a model based primarily on work in this species (Figure 5-36). Not unexpectedly, the "sheep" model cannot be extrapolated to all other mammals. Mechanisms of labor and parturition in goats, cattle, and swine do appear analogous to that of sheep.
The stimulus for initiation of labor and parturition in the ewe resides with the fetus - more specifically, the fetal anterior pituitary-adrenal axis. Fetal hypophysectomy or adrenalectomy prolongs gestation in the sheep. Infusion of fetal lambs with corticotropin-releasing hormone (CRH), ACTH, cortisol, or dexamethasone (a synthetic glucocorticoid) causes premature birth.
There is an elevation in the secretory rate of ACTH from the fetal anterior pituitary gland over the last month of gestation. The adrenal gland undergoes a striking increase in growth and responsiveness to ACTH during the last two weeks of pregnancy. There is a corresponding (cAMP-induced) rise in output of cortisol from the adrenal cortex (21- and 11b-hydroxylases convert 17a-hydroxyprogesterone). The late gestational increase in pituitary secretion of ACTH and maturation of the adrenal gland are timed genetically.
The site of action of cortisol is the placenta; it stimulates enzymatic syntheses (17a-hydroxylase, aromatase) resulting in a shift in steroidogenesis favoring the delta-5 pathway (progesterone declines/estradiol increases).
Estradiol promotes uterine contractility by increasing myometrial synthesis of contractile proteins, placental and endometrial synthesis of prostaglandins, myometrial receptors for oxytocin, and formation of gap junctions (ie., synthesis of connexins) between myometrial cells. Estradiol decreases the consistency of cervical mucus (liquefaction of the cervical plug) and sensitizes target tissues to relaxin.
Prostaglandin F2a augments myometrial contractility by liberating intracellular stores of calcium, and indirectly, by causing lysis of the CL (withdrawal of maternal progesterone). Prostaglandins are also involved directly in cervical ripening/softening (PGE2) and cause secretion of relaxin from the CL and(or) placenta (PGF2a). Uterine distension and irritation activates local production of prostaglandins.
As the uterus begins to contract and the fetus descends upon the cervix, neural signals are sent to the brain causing secretion of oxytocin (Ferguson's reflex). Oxytocin stimulates myometrial contractility by lowering the threshold for the generation of action potentials and induces intracellular influx of calcium. A positive feedback cycle is propagated as contractility becomes more intense and there is more release of oxytocin. The uterus can become exhausted to stimulation if birth does not occur (eg., the cervix does not dilate properly) within a restricted time; this is a repercussion of down-regulation of receptors.
Relaxin causes dissolution of bundles of collagen fibers and depolymerization of ground substance within the cervix and pubic symphysis. Relaxin has a pacemaker-like effect on myometrial rhythmicity; it acts to coordinate contractions induced by estradiol, prostaglandins, and oxytocin so they progress toward the cervix.
Other species/theories. It is questionable whether the fetal anterior pituitary-adrenal axis has an obligatory role in the signaling apparatus of labor in primates (although exogenous glucocorticoids are of some use in inducing delivery in extended pregnancies). High glucocorticoid levels at parturition in primates may reduce placental expression of extracellular matrix (adhesive) proteins that leads to separation of the placenta from the endometrium. Placenta are delivered at normal term after fetectomy in rabbits and rats. The key to initiation of labor in primates, rabbits, and rodents is evidently related to a genetically-determined maturational event intrinsic to the placenta (eg., increased production of estradiol or prostaglandins).
In many species parturition is correlated with a decrease in the ratio of progesterone to estrogen; this relationship is not universal - maternal systemic progesterone remains elevated in primates until the placenta is delivered.
Prostaglandin E2 stimulates uterine contractility in some species; in primates PGE2 is more potent than PGF2a.
Levels of plasma b-endorphin increase during labor. It is believed that opiates are involved in the control of pain associated with delivery. Whether endogenous opiates also participate directly in the mechanics of parturition is possible.
Nonendocrine theories of labor and parturition have been proposed. It has been suggested, for example, that delivery of the fetus is the result of a maternal immunological reaction (ie., the fetus is recognized near term as foreign and is rejected).