It is intriguing to envision that the mature human fetus provides the signal to initiate parturition, and evidence for fetal signaling is mounting (Mendelson, 2017). The fetus may give signals through blood-borne agents that act on the placenta or through secretion into the amnionic luid.
Fetal growth is an important component in uterine activation in phase 2 of parturition. With uterine activation, stretch is required for induction of specific CAPs. Namely, stretch increases expression of connexin-43 and oxytocin receptors. Levels of gastrin-releasing peptide, a stimulatory agonist for smooth muscle, are also augmented by stretch in the myometrium (Tattersall, 2012).
Clinical clues for a role of stretch come from the observa preterm labor than singleton ones. And, preterm labor is also signiicantly more common in pregnancies complicated by hydramnios. Although the mechanisms causing preterm birth in these two examples are debated, a role for uterine stretch must be considered.
Cell signaling systems that are inluenced by stretch to regulate the myometrial cell continue to be defined. his processmechanotransduction-may include activation of cell-surface receptors or ion channels, transmission of signals through extracellular matrix, or release of autocrine molecules that act directly on myometrium (Shynlova, 2007; Young, 2011).
The ability of the fetus to provide endocrine signals that initiate parturition has been demonstrated in several species. However, evidence suggests that it is not regulated in the same manner in humans. hat said, the human fetal hypothalamic-pituitaryadrenal-placental axis is considered a critical component of normal parturition. Moreover, premature activation of this axis is considered to prompt many cases of pre term labor (Challis, 2000, 2001). As in the sheep, steroid products of the human fetal adrenal gland are believed to have efects on the placenta and membranes that eventually transform the myometrium from a quiescent to a contractile state. A key component in the human may be the unique ability of the placenta to produce large amounts ofCRH 21-10).
A CRH hormone that is identical to maternal and fetal hypothalamic CRH is synthesized by the placenta in relatively large amounts (Grino, 1987; Saijonmaa, 1988). However, unlike hypothalamic CRH, which is under glucocorticoid negative feedback, cortisol instead stimulates placental CRH production. This ability makes it possible to create a feed-forward endocrine cascade that does not end until delivery.
Maternal plasma CRH levels are low in the first trimester and rise from midgestation to term. In the last 12 weeks, CRH plasma levels rise exponentially, peak during labor, and then fall precipitously after delivery (Frim, 1988; Sasaki, 1987). Amnionic luid CRH concentrations similarly increase in late gestation. CRH is the only trophic hormone-releasing
FIGURE 21-10 The placental-fetal adrenal endocrine cascade.
In late gestation, placental corticotropin-releasing hormone (CRH) stimulates fetal adrenal production of dehydroepiandrosterone sul fate (DHEA-S) and cortisol. The latter stimulates production of placental CRH, which leads to a feed-forward cascade that enhances adrenal steroid hormone production. ACTH = adrenocorticotropic hormone.
factor to have a speciic serum binding protein. During most of pregnancy, CRH-binding protein (CRH-BP) binds most maternal circulating CRH, and this inactivates it (Lowry, 1993). During later pregnancy, however, CRH-BP levels in both maternal plasma and amnionic luid decline, leading to markedly greater levels of bioavailable CRH (Perkins, 1995;