Abstract:

Background: Preterm labour, a condition characterized by regular uterine contractions and cervical dilation prior to 37 weeks of pregnancy can result in premature birth of babies that may not be fully developed and/or possess serious health problems such as cerebral palsy and learning disabilities. Is associated with an increase in uterine prostaglandins (PGs) synthesis by cyclooxygenase (COX) enzymes which promotes inflammatory and contractile processes that drive labour. For this reason, COX inhibitors (e.g. indomethacin) have been used to treat/prevent preterm labour. Despite limited success, tocolysis by COX-inhibition carries serious adverse fetal effects due to inhibition of prostaglandin-dependent developmental homeostatic functions. The more recent discovery of a second, inducible COX isoform, COX-2, presented an opportunity to spare homeostatic prostaglandin by selective inhibition of COX-2. However, subsequent clinical studies have called into question the appropriateness of COX-2 selective inhibition. This study reviewed the molecular evidence concerning the role of COX-2 in human parturition that underpins the rationale of use of COX-2 inhibitors in the treatment of preterm labour and presents evidence of COX-2 gene expression in term and preterm human myometrium.

Methods: For our systematic literature review, we searched MEDLINE and EMBASE databases to identify papers reporting molecular evidence of COX enzyme expression and activity in gestational tissues at term and preterm. Two independent reviewers evaluated abstracts, and qualifying references were reviewed in full text. Data were extracted using a standardized questionnaire. COX-2 gene expression analysis was conducted on samples of myometrium and decidua from women at term (after 37 weeks) and preterm (below 37 weeks) of gestation, with and without labour using reverse transcriptase-polymerase chain reaction technique (RT-PCR).

Results: Thirty-five studies were included in the review. Eight studies on fetal membranes (amnion and chorion) reported significantly higher COX expression or activity with labour. However, in the myometrium and decidua, which are the most relevant therapeutic target tissues for uterine contraction, nine reported no labour-associated differences COX expression. In the myometrium, four studies reported higher levels of COX mRNA with labour, but did not consider protein expression. Our data show spatial (upper versus lower segment) and temporal (labour versus non-labour) demonstrate differences in COX-2 expression; at term, expression of COX-2 is higher in lower segment myometrium and decidua samples from women in term labour (n=16) compared to term non-labour (n=18), but no significant differences were observed for upper segment samples. Similarly, COX-2 expression was higher in lower segment preterm labour