Petraglia, 1997).
In pregnancies in which the fetus can be considered "stressed" from various complications, concentrations of CRH in fetal plasma, amnionic luid, and maternal plasma are greater than those seen in normal gestation (Berkowitz, 1996; McGrath, 2002). he placenta is the likely source of this elevated CRH concentration. For example, placental CRH content is four fold higher in placentas from women with preeclampsia than in those from normal pregnancies (Perkins, 1995).
Placental CRH is thought to play several roles in parturition regulation. It may enhance fetal cortisol production to provide positive feedback so that the placenta produces more CRH. Late in pregnancy-phase 2 or 3 of parturition-modiication in the CRH receptor favors a switch from cAMP formation to increased myometrial cell calcium levels via protein kinase C activation (You, 2012). Oxytocin acts to attenuate CRHstimulated accumulation of cAMP in myometrial tissue. CRH acts to augment myometrial contractile force in response to PGF2: (Benedetto, 1994). Finally, CRH stimulates fetal adrenal Cwsteroid synthesis, thereby increasing substrate for placental aromatization.
Some have proposed that the rising CRH level at the end of gestation relects a etal-placental clock (McLean, 1995). CRH concentrations vary greatly among women, and the rate of rise in maternal CRH levels is a more accurate predictor of pregnancy outcome than is a single measurement (Leung, 2001; McGrath, 2002). In this regard, the placenta and fetus, through endocrinological events, inluence the timing of parturition at the end of normal gestation.
Surfactant protein A (SP-A) produced by the fetal lung is required for lung maturation. SP-A is expressed by the human amnion and decidua, is present in the amnionic luid, and prompts signaling pathways in human myometrial cells (Garcia-Verdugo, 2008; Lee, 2010; Snegovskikh, 2011). he exact mechanisms by which SP-A activates myometrial contractility in women, however, remain to be clarified. One mode may be its efects on prostaglandins. Namely, SP-A selectively inhibits prostaglandin F2: in the term decidua, but SP-A levels drop in the amnionic luid at term (Chaiworapongsa, 2008). In addition to SP-A, the fetal lung makes the uterotonic agent platelet-activating factor (Frenkel, 1996; T oyoshima, 1995). This factor and SP-A playia role in fetal-maternal signaling for parturition (Gao, 2015).
Toward the end of pregnancy, fetal membranes undergo physiological aging termed cellular senescence (Menon, 2016). In human fetal membranes and animal models, stretch and oxidative stress induce senescent fetal membrane to manifest a form of sterile inflammation termed senescent-associated secretory
Physiology of Labor 41s1 phenotype (SASP). This in turn propagates inlammatory signals that further weaken the fetal membrane and activate signals in the decidua and myometrium to initiate parturition. hus, as the functional necessity of fetal membranes declines at term, they are able to promote signals that contribute to parturition initiation.
Some evidence shows that pregnancies with markedly diminished estrogen production may be associated with prolonged gestation. These "natural experiments" include women with inherited placental sulfatase deiciency and fetal anencephaly with adrenal hypoplasia. The broad range of gestational length seen with these disorders, however, calls into question the exact role of estrogen in human parturition initiation.