The control of prostaglandin endoperoxide H-Synthase-2 expression in the human chorion laeve at term.
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.


CONCLUSIONS
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.
Johnson
Renée F
RF
Division of Obstetrics and Gynaecology, John Hunter Hospital, Newcastle, Australia.
Mitchell
Carolyn M
CM
Giles
Warwick B
WB
Walters
William A
WA
Zakar
Tamas
T
D002823:Chorion / Q000201:enzymology*; D051546:Cyclooxygenase 2; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D007743:Labor, Obstetric / Q000378:metabolism*; D008565:Membrane Proteins; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D020871:RNA Stability / Q000502:physiology; D012332:RNA, Heterogeneous Nuclear / Q000737:chemistry / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000502:physiology
D007527:Isoenzymes; D008565:Membrane Proteins; D012332:RNA, Heterogeneous Nuclear; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases