Definition of the myometrial transcriptome and proteome of preterm labour of known and unknown aetiologies versus term labour: elucidation of common vs. distinct regulatory pathways

Abstract

Term labour (TL) is a complex interplay of maternal and fetal factors which maintains the uterus in a state of quiescence during pregnancy, and then subsequently converts the uterus into a contractile organ which aids to expel the baby. Preterm labour (PTL) is not a single entity but is now recognised as multifactorial disorder and not just the early onset of TL. The aim of this study was to examine the similarities and differences in the molecular pathways of both TL and PTL. Myometrial samples were collected at the time of caesarean section from women in no labour (preterm singleton, preterm twins and term), term early labour, term established labour and PTL (placental abruption, chorioamnionitis PTL, idiopathic PTL and Twins PTL) were used to study pro-labour gene expression using quantitative rtPCR and protein levels/concentrations using Western blotting and multiplexed cytokine assays. Increasing gestation was associated with increased OTR, CX-43, PGDS, PGES-1 and PGES-2 but a decrease in PGFS, PGIS, SRC3 and FKBP5. At the onset of TL (term early labour samples), mRNA expression of PGHS-2 and SRC3 increased while both mRNA expression and protein levels of PGDS, PGIS and PR-B decreased compared to term no labour (TNL). None of the inflammatory chemokines were increased at the onset of term labour compared to TNL. Established labour was associated with a decrease in PGHS-2 (mRNA), increased PGFS and a higher protein concentration of IL-1β, IL-4, IL-6, IL-8, IL-10, CCL-1, CCL-11, CCL-24, CXCL-1, CXCL-5 and CXCL-6 compared to TNL and term early labour. In the preterm labour phenotypes, chorioamnionitis PTL was associated with increased PGHS-2 (mRNA), OTR, PGES-2 and 14 cytokines but a decreased PGDS and CS-43 compared to preterm no labour (PTNL). In contrast, idiopathic PTL, polyhydramnios and abruption PTL was not associated with an increase in cytokines and showed different prolabour gene profiles compared to each other. PTL associated with twins had a less intense inflammatory profile than chorioamnionits PTL. The prolabour gene and inflammatory profile of TL differs in comparison to each of the PTL phenotypes. The inflammation in the myometrium in TL is a consequence rather than the cause of labour while that in PTL is most likely involved in the onset of PTL in phenotypes such as chorioamnionitis or twins PTL.