title: Hypoxyprobe™ reveals dynamic spatial and temporal changes in hypoxia in a mouse model of endometrial breakdown and repair.
abstract: BACKGROUND
  Menstruation is the culmination of a cascade of events, triggered by the withdrawal of progesterone at the end of the menstrual cycle. Initiation of tissue destruction and endometrial shedding causes spiral arteriole constriction in the functional layer of the endometrium. Upregulation of genes involved in angiogenesis and immune cell recruitment, two processes that are essential to successful repair and remodelling of the endometrium, both thought to be induced by reduced oxygen has been reported. Evidence for stabilisation/increased expression of the transcriptional regulator hypoxia inducible factor in the human endometrium at menses has been published. The current literature debates whether hypoxia plays an essential role during menstrual repair, therefore this study aims to delineate a role for hypoxia using a sensitive detection method (the Hypoxyprobe™) in combination with an established mouse model of endometrial breakdown and repair.
  
  
  RESULTS
  Using our mouse model of menses, during which documented breakdown and synchronous repair occurs in a 24 h timeframe, in combination with the Hypoxyprobe™ detection system, oxygen tensions within the uterus were measured. Immunostaining revealed striking spatial and temporal fluctuations in hypoxia during breakdown and showed that the epithelium is also exposed to hypoxic conditions during the repair phase. Furthermore, time-dependent changes in tissue hypoxia correlated with the regulation of mRNAs encoding for the angiogenic genes vascular endothelial growth factor and stromal derived factor (Cxcl12).
  
  
  CONCLUSIONS
  Our findings are consistent with a role for focal hypoxia during endometrial breakdown in regulating gene expression during menses. These data have implications for treatment of endometrial pathologies such as heavy menstrual bleeding.
authors.affiliation: Medical Research Council Centre for Inflammation Research, The University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK. Fiona.Cousins@ed.ac.uk.
authors.forename: Fiona L
authors.initials: FL
authors.lastname: Cousins
authors.affiliation: Medical Research Council Centre for Reproductive Health, The University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK. Alison.Murray@ed.ac.uk.
authors.forename: Alison A
authors.initials: AA
authors.lastname: Murray
authors.affiliation: Medical Research Council Centre for Inflammation Research, The University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK. s0787100@exseed.ed.ac.uk.
authors.forename: Jessica P
authors.initials: JP
authors.lastname: Scanlon
authors.affiliation: Medical Research Council Centre for Inflammation Research, The University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK. p.saunders@ed.ac.uk.
authors.forename: Philippa T K
authors.initials: PT
authors.lastname: Saunders
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12 / Q000235:genetics* / Q000378:metabolism; D004717:Endometrium / Q000098:blood supply / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008598:Menstruation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000235:genetics*; D011374:Progesterone / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
chemical_list: D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D011374:Progesterone