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The Control of Prostaglandin Endoperoxide H-Synthase-2 Expression in the Human Chorion Laeve at Term

Carolyn M. Mitchell, BSc

Warwick B. Giles, MBBS, PhD

William A. Walters, MBBS, PhD

Division of Obstetrics and Gynaecology, John Hunter Hospital, Newcastle, Australia; Discipline of Reproductive Medicine,, and Mothers and Babies Research Centre, University of Newcastle, Newcastle, Australia

Tamas Zakar, MD, PhD

Division of Obstetrics and Gynaecology, Mothers and Babies Research Centre, John Hunter Hospital, Locked Bag 1, Hunter Region Mail Centre, Newcastle NSW 2310 Australia; tzakar{at}mail.newcastle.edu.au

Objective: Prostaglandin endoperoxide H synthase-2 (PGHS-2), the key enzyme of prostaglandin biosynthesis in gestational tissues, is expressed in the chorion laeve at term. We have determined the mechanisms that control the level of PGHS-2 mRNA in the chorion membrane in order to assess the significance of chorion-derived prostaglandins in term labor.

Methods: Chorion membranes were collected after elective cesarean delivery (CD, n = 21) and after spontaneous labor (SL, n = 20) at term. The PGHS-2 gene transcription rate was measured by transcriptional run-on, and PGHS-2 mRNA and heterogeneous RNA (hnRNA) abundance was determined by quantitative real-time reverse transcriptase polymerase chain reaction. PGHS-2 mRNA stability, PGHS-2 hnRNA processing rate, and the short-term dynamics of the two RNA species were characterized in 0-24-hour-long tissue incubations.

Results: The transcriptional activity of the PGHS-2 gene predicted (P < .02) the abundance of PGHS-2 mRNA and hnRNA in individual tissues. PGHS-2 gene activity and hnRNA processing rate were not different in the CD and SL groups. PGHS-2 mRNA was constitutively stable before and after labor, and its abundance spontaneously increased sixfold in tissues incubated for 24 hours. At the same time, PGHS-2 gene activity decreased by 80% within 2 hours and rebounded to 60% of its initial level by 24 hours.

Conclusion: PGHS-2 mRNA is highly stable, and its abundance is transcriptionally controlled in the chorion laeve at term. Labor is not associated with changing PGHS-2 gene activity. Endogenous factors drive PGHS-2 gene transcription in the chorion, and the stable PGHS-2 mRNA accumulates in the tissue at term. This accumulation has little or no impact on the timing of labor.

Key Words: Chorion • PGHS-2 mRNA • term

Journal of the Society for Gynecologic Investigation, Vol. 10, No. 4, 222-230 (2003)
DOI: 10.1016/S1071-55760300046-7


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