2002 IRISH SCIENTIST YEAR BOOK

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Health Research Board & National University of Ireland, Galway
John J. Morrison
COX-2 and human labour – term and preterm

Meloxicam – Tissue Bath Concentration Uterine smooth muscle – in labour.

The factors regulating the onset of labour in the human are poorly understood. Despite this, abnormalities in the onset of labour constitute a significant problem in obstetric practice, paediatric practice and for long term problems in childhood development. Preterm or premature labour occurs in 6–10% of the population. Babies born preterm require long periods of stay in the neonatal intensive care unit and are at risk of long term developmental disabilities. In addition, the cost of hospital and community care for infants born prematurely is a major expense for health service providers.

It is well established that prostaglandins are closely linked to the onset and maintenance of human labour. Prostaglandins are formed by way of the cycloxygenase (COX enzymes). There are two isoforms of the cyclooxygenase enzymes, COX-1 and COX-2. They are both encoded by different genes. It is believed that COX-2 plays a more central role in the onset of human labour. This project, which was funded by the HRB, was designed with the following objectives:

  1. To investigate expression of COX-2 in placenta and fetal membranes at the time of human labour.

  2. To investigate the effects of COX-2 inhibition on human pregnant myometrial (uterine) contractility.

  3. To examine the hypothesis that COX-2 inhibitors, which exhibit varying COX-2 selectivity, may have a varying effect on contractile activity of human myometrium.

Using RT-PCR (reverse transcriptase polymerase chain reaction), we have identified and quantified COX-2 expression in human amnion, chorion and placenta. The messenger RNA levels identified, at different periods of gestation, before and after labour onset, revealed no significant COX-2 expression in these tissues. The COX-2 inhibitors nimesulide, meloxicam and celecoxib all exerted a significant relaxant effect on contractility of human myometrium in vitro. An in vitro recording of smooth muscle contractility from a uterine biopsy obtained from caesarean section during labour is demonstrated in the Figure. A cumulative and potent relaxing effect was observed. The COX-2 specific inhibitor celecoxib was more potent than the COX-2 preferential inhibitors, nimesulide or meloxicam.

Data from this kind of scientific study are essential to finding solutions to the problem of premature labour and its significant clinical sequelae (Slattery M.M., Friel A.M., Healy D.G., Morrison J.J., Uterine relaxant effects of Cyclooxygenase-2 inhibitors in vitro. Obstet Gynaecol, 2001, 98, 563-569).

Participants: Professor John J. Morrison, Professor of Obstetrics and Gynaecology; Professor Terry Smith, Professor of Biomedical Engineeering Science; Ms Anne M. Friel, PhD Student (funded for two years by HRB); Dr Michael M. Slattery, SHO, Obstetrics and Gynaecology.
Contact: Professor John J. Morrison, Professor of Obstetrics and Gynaecology,
Clinical Science Institute,
National University of Ireland, Costello Road, Galway;