title: Genes responsible for vaginal extracellular matrix metabolism are modulated by women's reproductive cycle and menopause.
abstract: OBJECTIVE
  To analyze the expression of genes involved in extracellular matrix (ECM) biogenesis and remodeling in vaginal tissue of women with clinically normal pelvic floor support (defined as controls) according to the phase of menstrual cycle and postmenopausal women with and without pelvic organ prolapse (POP).
  
  
  METHODS
  This study examined the expression of matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and the Lysyl oxidase (LOX) family genes in the anterior vaginal wall of Caucasian women by real-time RT-PCR. Initially, mRNA expression was assessed in premenopausal controls in the secretory (group 1, n = 10) vs. proliferative (group 2, n = 8) phase of menstrual cycle. In addition, we compared premenopausal controls in the proliferative phase (group 2) vs. postmenopausal controls (group 3, n = 5). Finally, we analyzed postmenopausal controls (group 3) vs. postmenopausal women with advanced POP (group 4, n = 13).
  
  
  RESULTS
  According to the phase of menstrual cycle, MMP1 was significantly reduced (p = 0.003), whereas the expression of TIMP1 and LOXL4 was significantly up-regulated during proliferative phase (both p < 0.01) when compared to the secretory phase in premenopausal control women. Regarding menopausal status/ageing, all MMPs were down-regulated, while TIMP3, TIMP4 and LOXL2 were significantly up-regulated in postmenopausal control women when compared to premenopausal controls (p = 0.005, p = 0.01 and p < 0.001, correspondingly). TIMP4 and LOXL2 mRNA levels were significantly decreased in postmenopausal POP patients compared to asymptomatic postmenopausal controls (p < 0.01 for both).
  
  
  CONCLUSIONS
  Our results indicate that ovarian cycle and age-related changes influence the expression of genes encoding proteins responsible for ECM metabolism in human vagina. Moreover, POP is associated with alteration in vaginal ECM components after menopause.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada. shynlova@lunenfeld.ca
authors.forename: Oksana
authors.initials: O
authors.lastname: Shynlova
authors.forename: Maria A T
authors.initials: MA
authors.lastname: Bortolini
authors.forename: May
authors.initials: M
authors.lastname: Alarab
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D016022:Case-Control Studies; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D008593:Menopause / Q000235:genetics* / Q000378:metabolism; D008597:Menstrual Cycle / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D017697:Premenopause / Q000235:genetics / Q000378:metabolism; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D014621:Vagina / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D004549:Elastin; D008249:Protein-Lysine 6-Oxidase; D020782:Matrix Metalloproteinases