Identification of 9α,11β-Prostaglandin F2 in Human Amniotic Fluid and Characterization of Its Production by Human Gestational Tissues

Abstract

9alpha,11beta-Prostaglandin F(2) (9alpha,11beta-PGF(2)) can contract uterine smooth muscle with a potency equal to PGF(2alpha). Its presence in the human uterus and production by human gestational tissues is unknown. These studies were performed to determine whether the PGD(2)-derived 9alpha,11beta-PGF(2) is both present in human amniotic fluid and synthesized by human gestational tissues and if so, whether labor-related substances could regulate its production. Detectable concentrations of 9alpha,11beta-PGF(2) were found in amniotic fluid samples and appeared to increase in late gestation. All gestational tissues studied synthesized 9alpha,11beta-PGF(2), with the placenta having the highest basal production rate, followed by the amnion and then the choriodecidua. IL-1beta and TNFalpha caused concentration-dependent increases in 9alpha,11beta-PGF(2) production in human amnion and choriodecidual explants. Moreover, treatment of choriodecidual and placental explants with lipopolysaccharide resulted in a significant increase in 9alpha,11beta-PGF(2) production rates, reaching a maximum of 13-fold in the choriodecidua. Studies examining the effects of the addition of exogenous PGD(2) strongly indicated that the choriodecidua has significant ability to convert PGD(2) to 9alpha,11beta-PGF(2), whereas the amnion has little. These results demonstrate for the first time that 9alpha,11beta-PGF(2) is present in human amniotic fluid and that it is produced by human gestational tissues and up-regulated by bacterial cell wall components and proinflammatory cytokines. We suggest that this prostaglandin may play a part in the mechanisms of human labor at term and preterm.