AbstractContext: 9α,11β-Prostaglandin F2 (9α,11β-PGF2) can contract uterine smooth muscle with a potency equal to PGF2α. Its presence in the human uterus and production by human gestational tissues is unknown.Objective: These studies were performed to determine whether the PGD2-derived 9α,11β-PGF2 is both present in human amniotic fluid and synthesized by human gestational tissues and if so, whether labor-related substances could regulate its production.Results: Detectable concentrations of 9α,11β-PGF2 were found in amniotic fluid samples and appeared to increase in late gestation. All gestational tissues studied synthesized 9α,11β-PGF2, with the placenta having the highest basal production rate, followed by the amnion and then the choriodecidua. IL-1β and TNFα caused concentration-dependent increases in 9α,11β-PGF2 production in human amnion and choriodecidual explants. Moreover, treatment of choriodecidual and placental explants with lipopolysaccharide resulted in a significant increase in 9α,11β-PGF2 production rates, reaching a maximum of 13-fold in the choriodecidua. Studies examining the effects of the addition of exogenous PGD2 strongly indicated that the choriodecidua has significant ability to convert PGD2 to 9α,11β-PGF2, whereas the amnion has little.Conclusions: These results demonstrate for the first time that 9α,11β-PGF2 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.