title: The study of progesterone action in human myometrial explants.
abstract: Myometrial explants represent a superior model compared with cell culture models for the study of human myometrial progesterone (P4) signalling in parturition.
  
  
  
  Gene expression analysis showed myometrial explants closely resemble the in vivo condition and the anti-inflammatory action of P4 is not lost with labour onset.
  
  
  
  Circulating P4 levels decline before the onset of parturition in most animals, but not in humans. This has led to the suggestion that there is a functional withdrawal of P4 action at the myometrial level prior to labour onset. However, to date, no evidence of a loss of P4 function has been provided, with studies hampered by a lack of a physiologically relevant model.
  
  
  
  Myometrial biopsies obtained at Caesarean section were dissected into explants after a portion was immediately snap frozen (t = 0). Microarray analysis was used to compare gene expression of t = 0 with paired (i) explants, (ii) passage 4 myometrial cell cultures or (iii) the hTERT myometrial cell line. Western blotting and chemokine/cytokine assays were used to study P4 signalling in myometrial explants.
  
  
  
  Gene expression comparison of t = 0 to the three models demonstrated that explants more closely resemble the in vivo status. At the protein level, explants maintain both P4 receptor (PR) and glucocorticoid receptor (GR) levels versus t = 0 whereas cells only maintain GR levels. Additionally, treatment with 1 µM P4 led to a reduction in interleukin-1 (IL-1) β-driven cyclooxygenase-2 in explants but not in cells. P4 signalling in explants was PR-mediated and associated with a repression of p65 and c-Jun phosphorylation. Furthermore, the anti-inflammatory action of P4 was maintained after labour onset.
  
  
  
  There is evidence of basal inflammation in the myometrial explant model.
  
  
  
  Myometrial explants constitute a novel model to study P4 signalling in the myometrium and can be used to further elucidate the mechanisms of P4 action in human labour.
  
  
  
  Data deposited at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=gvmpggkurbgxfqf&acc=GSE77830.
  
  
  
  This work was supported by grants from the Joint Research Committee of the Westminster Medical School Research Trust, Borne (No. 1067412-7; a sub-charity of the Chelsea and Westminster Health Charity) and the Imperial NIHR Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS or the Department of Health. The authors have no conflict of interest.
authors.affiliation: Imperial College Parturition Research Group, Department of Obstetrics and Gynecology, Imperial College School of Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: E X
authors.initials: EX
authors.lastname: Georgiou
authors.affiliation: Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: K
authors.initials: K
authors.lastname: Lei
authors.affiliation: Imperial College Parturition Research Group, Department of Obstetrics and Gynecology, Imperial College School of Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK.
authors.forename: P F
authors.initials: PF
authors.lastname: Lai
authors.affiliation: Imperial College Parturition Research Group, Department of Obstetrics and Gynecology, Imperial College School of Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: A
authors.initials: A
authors.lastname: Yulia
authors.affiliation: Imperial College Parturition Research Group, Department of Obstetrics and Gynecology, Imperial College School of Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK.
authors.forename: B R
authors.initials: BR
authors.lastname: Herbert
authors.affiliation: Nottingham Arabidopsis Stock Centre, Plant Science Building, School of Biosciences, Sutton Bonington Campus, University of Nottingham, Loughborough LE12 5RD, UK.
authors.forename: M
authors.initials: M
authors.lastname: Castellanos
authors.affiliation: Nottingham Arabidopsis Stock Centre, Plant Science Building, School of Biosciences, Sutton Bonington Campus, University of Nottingham, Loughborough LE12 5RD, UK.
authors.forename: S T
authors.initials: ST
authors.lastname: May
authors.affiliation: Imperial College Parturition Research Group, Department of Obstetrics and Gynecology, Imperial College School of Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Sooranna
authors.affiliation: Imperial College Parturition Research Group, Department of Obstetrics and Gynecology, Imperial College School of Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK mark.johnson@imperial.ac.uk.
authors.forename: M R
authors.initials: MR
authors.lastname: Johnson
mesh_terms: D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009215:Myometrium / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D011374:Progesterone; D051546:Cyclooxygenase 2
keywords: hTERT; myometrial cells; myometrial explants; nuclear receptors; parturition; progesterone withdrawal; smooth muscle