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This version published online on April 19, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-2496
A more recent version of this article appeared on July 1, 2005
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Submitted on December 20, 2004
Accepted on April 7, 2005

Identification of 9{alpha},11{beta}-Prostaglandin F2 in Human Amniotic Fluid and Characterization of its Production by Human Gestational Tissues

MURRAY D. MITCHELL*, MAXWELL C. CHANG, TINNAKORN CHAIWORAPONGSA, HAO-YI LAN, RACHEL J.A. HELLIWELL, ROBERTO ROMERO, and TIMOTHY A. SATO

Liggins Institute, University of Auckland, & National Research Centre for Growth and Development, Private Bag 92019, Auckland, New Zealand and Perinatal Research Branch, NICHD, Detroit, Michigan

* To whom correspondence should be addressed. E-mail: m.mitchell{at}auckland.ac.nz.

Context: 9{alpha},11{beta}-Prostaglandin F2 (9{alpha},11{beta}-PGF2) can contract uterine smooth muscle with a potency equal to PGF2{alpha}. 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 9{alpha},11{beta}-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 9{alpha},11{beta}-PGF2 were found in amniotic fluid samples and appeared to increase in late gestation. All gestational tissues studied synthesized 9{alpha},11{beta}-PGF2 with the placenta having the highest basal production rate followed by the amnion and then the choriodecidua. Interleukin-1{beta} (IL-1{beta}) and tumor necrosis factor-{alpha} (TNF-{alpha}) caused concentration-dependent increases in 9{alpha},11{beta}-PGF2 production in human amnion and choriodecidual explants. Moreover treatment of choriodecidual and placental explants with lipopolysaccharide (LPS) resulted in a significant increase in 9{alpha},11{beta}-PGF2 production rates reaching a maximum of 13-fold in the choriodecidua. Studies examing the effects of the addition of exogenous PGD2 strongly indicated that the choriodecidua has significant ability to convert PGD2 to 9{alpha},11{beta}-PGF2, while the amnion has little.

Conclusions: These results demonstrate for the first time that 9{alpha},11{beta}-PGF2 is present in human amniotic fluid and that it is produced by human gestational tissues and upregulated by bacterial cell wall components and pro-inflammatory cytokines. We suggest that this prostaglandin may play a part in the mechanisms of human labor at term and preterm.


Key words: 9{alpha} • 11{beta}-PGF2 • Inflammatory mediators • Human gestational tissues







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