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1 Division of Obstetrics and Gynaecology, John Hunter Hospital, Newcastle, New South Wales, Australia
2 Discipline of Reproductive Medicine, University of Newcastle, Newcastle, New South Wales, Australia
3 Mothers and Babies Research Centre, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
(Requests for offprints should be addressed to T Zakar; Division of Obstetrics and Gynaecology, Mothers and Babies Research Centre, John Hunter Hospital, Locked Bag 1, Hunter Region Mail Centre, Newcastle, N.S.W. 2310 Australia; Email: tzakar{at}mail.newcastle.edu.au)
Increasing prostaglandin H2 synthase (PGHS)-2 expression in the fetal membranes is implicated in the production of prostaglandins (PGs) that stimulate labour. We have determined the activity of the PGHS-2 gene in the amnion and chorion throughout gestation and defined the contribution of transcriptional and post-transcriptional mechanisms to the increase of PGHS-2 mRNA levels. We also measured PGHS-1 mRNA abundance to assess the participation of the two isoenzymes in fetal membrane PG-production during pregnancy. Amnion and chorion were collected from non-labouring women at 1019 weeks (early), at 2836 weeks (preterm) and at term (3741 weeks). We determined PGHS-1 and -2 mRNA abundance and assessed PGHS-2 gene activity by measuring PGHS-2 heterogeneous nuclear RNA levels using real-time RT-PCR. PGHS-2 gene activity and mRNA levels were up-regulated in both tissues with advancing gestation. Path analysis demonstrated that the PGHS-2 mRNA up-regulation involved both transcriptional and post-transcriptional components. PGHS-2 mRNA abundance increased 911 fold between the early (1019 weeks) and preterm (2836 weeks) groups and remained high at term. The underlying mechanism was predominantly transcriptional in the amnion and post-transcriptional in the chorion. PGHS-1 mRNA expression precipitously decreased between early gestation and term. Thus, PGHS-2 mRNA abundance is up-regulated well in advance of term and is not a trigger for labour. There is a switch in PGHS mRNA expression during pregnancy with PGHS-1 dominating in the early period and PGHS-2 dominating at term.
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C.M. Mitchell, R.F. Johnson, W.B. Giles, and T. Zakar Prostaglandin H synthase-2 gene regulation in the amnion at labour: histone acetylation and nuclear factor kappa B binding to the promoter in vivo Mol. Hum. Reprod., January 1, 2008; 14(1): 53 - 59. [Abstract] [Full Text] [PDF] |
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