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


OBJECTIVE
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.


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 PGD(2) 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.
Helliwell
Rachel J A
RJ
The Liggins Institute, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Keelan
Jeffrey A
JA
Marvin
Keith W
KW
Adams
Linda
L
Chang
Maxwell C
MC
Anand
Ashmit
A
Sato
Timothy A
TA
O'Carroll
Simon
S
Chaiworapongsa
Tinnakorn
T
Romero
Roberto J
RJ
Mitchell
Murray D
MD
D000653:Amniotic Fluid / Q000201:enzymology / Q000378:metabolism; D015153:Blotting, Western; D049033:Chorioallantoic Membrane / Q000201:enzymology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D054834:Lipocalins; D010920:Placenta / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000235:genetics; D011453:Prostaglandins / Q000096:biosynthesis*; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics; D011982:Receptors, Prostaglandin / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D054834:Lipocalins; D011453:Prostaglandins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C037112:9-deoxy-delta-9-prostaglandin D2; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor