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Gestational Age-Dependent Up-Regulation of Prostaglandin D Synthase (PGDS) and Production of PGDS-Derived Antiinflammatory Prostaglandins in Human Placenta

Liggins Institute (R.J.A.H., J.A.K., K.W.M., L.A., M.C.C., A.A., T.A.S., S.O., M.D.M.), Department of Pharmacology and Clinical Pharmacology (J.A.K., S.O., M.D.M.), National Research Center for Growth and Development (M.D.M.), Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; and Perinatal Research Branch, National Institute of Child Health and Human Development, National Institutes of Health (T.C., R.J.R.), Detroit, Michigan 48201

Address all correspondence and requests for reprints to: Dr. Murray D. Mitchell, The Liggins Institute, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand. E-mail: m.mitchell{at}auckland.ac.nz.

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 PGD₂ 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 PGD₂ receptor identified to date, D prostanoid₁ (DP₁) and DP₂/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 PGD₂. In vitro, placental PGD₂ production was shown to be stimulated upon inflammatory activation, whereas PGD₂ 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.

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