title: Genes for prostaglandin synthesis, transport and inactivation are differentially expressed in human uterine tissues, and the prostaglandin F synthase AKR1B1 is induced in myometrial cells by inflammatory cytokines.
abstract: Prostaglandins (PGs) are important factors in the physiology of human parturition and the control of uterine contractility. We have characterized the expression of 15 genes from all stages of the PG pathway in human pregnant and non-pregnant (NP) myometrium and in other uterine tissues at delivery, and the results show patterns indicative of different capacities for PG synthesis and catabolism in each tissue. In placenta, the PG synthase expression profile favours production of PGD₂, PGE₂ and PGF₂, with high levels of PG transporters and catabolic PG dehydrogenase suggesting rapid PG turnover. Choriodecidua is primed for PGE₂, PGF₂ and PGD₂ production and high PG turnover, whereas amnion expresses genes for PGE₂ synthesis with low levels of PG transporters and dehydrogenase. In umbilical cord, PGI₂ synthase is highly expressed. In pregnant myometrium, PGI₂, PGD₂ and PGF₂ synthases are highly expressed, whereas PG dehydrogenase is underexpressed. Myometrium from women with spontaneous or induced labour had higher expression of the PGH₂ synthase PTGS2 than tissue from women not-in-labour. Myometrium from NP women had lower levels of PG synthases and higher levels of PG dehydrogenase than pregnant myometrium. Discriminant function analysis showed that expression of selected genes in myometrium could distinguish groups of women with different modes of labour from each other and from NP women. In cultured myometrial cells, there was a dose-dependent stimulatory effect of interleukin 1β and tumour necrosis factor α on PTGS2, PTGES and AKR1B1 (PGF synthase) expression.
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Clinical Science at South Bristol (Obstetrics and Gynaecology), University of Bristol, Dorothy Hodgkin Building, Bristol BS1 3NY, UK. r.j.phillips@bristol.ac.uk
authors.forename: R J
authors.initials: RJ
authors.lastname: Phillips
authors.forename: H
authors.initials: H
authors.lastname: Al-Zamil
authors.forename: L P
authors.initials: LP
authors.lastname: Hunt
authors.forename: M A
authors.initials: MA
authors.lastname: Fortier
authors.forename: A
authors.initials: A
authors.lastname: López Bernal
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000494:pharmacology; D008954:Models, Biological; D009215:Myometrium / Q000166:cytology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011453:Prostaglandins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014470:Umbilical Cord / Q000378:metabolism; D014599:Uterus / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D053583:Interleukin-1beta; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D006911:Hydroxyprostaglandin Dehydrogenases; C031051:prostaglandin-F synthase