Gestational age-dependent up-regulation of prostaglandin D synthase (PGDS) and production of PGDS-derived antiinflammatory prostaglandins in human placenta

Context: The importance of prostaglandin ( PG) signaling pathways to the maintenance of pregnancy and initiation of labor is well recognized. However, the complexity of these pathways and the mechanism(s) of their coordinated regulation in physiological and pathological conditions are only now being appreciated. Objectives: In this report we provide new evidence of a complete pathway for the biosynthesis and actions of PGD(2) and its metabolites within human gestational tissues. Materials and Methods: Using immunohistochemistry and Northern and Western blotting, we demonstrate the dynamic regulation of H-type PGD synthase (PGDS) in placenta during gestation; in contrast, L-type PGDS and its PG products were detected in amniotic fluid, with increased amounts associated with labor. Results: Placental tissues were shown to express both forms of the PGD(2) receptor identified to date, D prostanoid(1) (DP(1)) and DP(2)/chemotactic receptor on type 2 helper T cells, with a distribution consistent with the villous placenta being a major target, as well as source, of PGD(2). In vitro, placental PGD2 production was shown to be stimulated upon inflammatory activation, whereas PGD(2) and its J series metabolites exerted potent inhibitory effects on placental cytokine production. Conclusions: These findings suggest that PGDS-derived prostanoids play important physiological roles in the placenta, such as immunoregulation and feto-placental communication, while potentially having a regulatory role in the processes of parturition.