Author's response to reviews Title:Prostaglandin pathway gene expression in human placenta, amnion and choriodecidua is differentially affected by preterm and term labour and by uterine inflammation Authors:

79 Background 80 Elucidation of the biochemical pathways involved in activation of preterm and term human 81 labour would facilitate the development of effective management and inform judgements 82 regarding the necessity for preterm tocolysis and post-term induction. Prostaglandins act at 83 all stages of human reproduction, and are potentially activators of labour. 84 Methods 85 Expression of 15 genes involved in prostaglandin synthesis, transport and degradation was 86 measured by qPCR using tissue samples from human placenta, amnion and choriodecidua at 87 preterm and full-term vaginal and caesarean delivery. Cellular localisation of eight 88 prostaglandin pathway proteins was determined by immunohistochemistry. 89 Results 90 Expression of prostaglandin pathway genes was differentially affected by factors including 91 gestational age at delivery, and the incidence and duration of labour. 92 Chorioamnionitis/deciduitis was associated with upregulation of PTGS2 (prostaglandin93 endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)), along with the 94 inflammatory genes IL8 (interleukin 8), S100A8 (S100 calcium binding protein A8) and TLR2 95 (toll-like receptor 2), in amnion and choriodecidua, and with downregulation of CBR1 96 (carbonyl reductase 1) and HPGD (hydroxyprostaglandin dehydrogenase 15-(NAD)) in 97 choriodecidua. Protein localisation differed greatly between the various maternal and fetal 98 cell types. 99 Conclusions 100