Endothelin levels in human amniotic fluid at mid-trimester and at term before and during spontaneous labor

Endothelin (ET)-1 is synthesized in human amnion and immunoreactive (ir) ET is present in amniotic fluid in concentrations 10- to 100-times those found in plasma. ET-1 is a potent uterotonin; therefore, the possibility must be considered that ET-1, derived from amnion/amniotic fluid, serves to promote the uterine contractions of human labor. In term pregnancies, after labor begins, the amniotic fluid normally becomes divided into the upper and forebag compartments as the fetal presenting part is engaged in the maternal pelvis. The forebag tissues are exposed in the vagina because of cervical dilatation. Vaginal fluid contains microorganisms, bacterial toxins, and cytokines, e.g., interleukin-1β, that oblige an inflammatory reaction. Increased ET-1 formation in these tissues of the forebag would be indicative that the greater rate of ET-1 formation and entry into amniotic fluid was an aftereffect of labor, not a cause of parturition. The levels of irET in amniotic fluid during the midtrimester of human pregnancy, 93.3 ± 7.4 pmol/L (mean ± SEM, n=38), were significantly greater than those in amniotic fluid at term before the onset of labor, 39.8 ± 4.1 (n=33, p<0.01). The levels of irET in the upper compartment during labor, 45.5 ± 3.5 pmol/L (n=40), were not significantly different from those in amniotic fluid before labor, but were significantly less (p<0.01) than those in amniotic fluid of the forebag, 82.1 ± 5.2 pmol/L (n=125). These findings are suggestive that increases in the concentration of ET in amniotic fluid at parturition are confined to the forebag and are the result of ET formation after labor begins. Inflammation of the tissues lining the forebag compartment of the amniotic fluid is a normal consequence of labor. Therefore, the entry of inflammatory response mediators, some of which are uterotonins, viz., ET and prostaglandins, into forebag amniotic fluid is an aftereffect of labor and not indicative of a role for these agents (in amniotic fluid) in the initiation of parturition. In a subset of the amniotic fluids from normal pregnancies at term, prostaglandin (PG) levels also were determined. There was a highly significant correlation between the levels of irET and PGE2 in the forebag compartment (p<0.0001); there was no correlation between irET and PGE₂ levels in the upper compartment or in amniotic fluid collected at term prior to labor onset. There was no correlation between PGF_2α and PGFM in any of the amniotic fluid groups except for PGF_2α in the forebag (p<0.03). These findings are suggestive that the forebag tissue site(s) of origin of ET and PGE₂ are identical.