Histological and Gene Expression Analysis of the Effects of Menopause Status and Hormone Therapy on the Vaginal Introitus and Labia Majora.
Atrophy
Gene expression
Histology
Introitus
Labia majora
Menopause
Vagina
Journal
Journal of clinical medicine research
ISSN: 1918-3003
Titre abrégé: J Clin Med Res
Pays: Canada
ID NLM: 101538301
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
16
09
2019
accepted:
27
09
2019
entrez:
6
12
2019
pubmed:
6
12
2019
medline:
6
12
2019
Statut:
ppublish
Résumé
The study aimed to determine the effect of menopausal status and hormone therapy on the introitus and labia majora at the levels of histology and gene expression. Three cohorts of 10 women each (pre-menopause, post-menopause and post-menopause + hormone therapy) were selected based on the presentation of clinical atrophy and vaginal pH. Biopsies were obtained from the introitus (fourchette) and labia majora and processed for histology and gene expression analyses with microarrays. Other data collected included self-assessed symptoms, serum estradiol, testosterone, serum hormone binding globulin and the pH of the vagina and labia majora. The introitus appears exquisitely sensitive to hormone status. Dramatic changes were observed in histology including a thinning of the epithelium in post-menopausal subjects with vaginal atrophy. Furthermore, there was differential expression of many genes that may contribute to tissue remodeling in the atrophic introitus. Levels of expression of genes associated with wound healing, angiogenesis, cell migration/locomotion, dermal structure, apoptosis, inflammation, epithelial cell differentiation, fatty acid, carbohydrate and steroid metabolism were significantly different in the cohort exhibiting atrophy of the introitus. While changes were also observed at the labia, that site was considerably less sensitive to hormone status. The gene expression changes observed at the introitus in this study were very similar to those reported previously in the atrophic vagina providing further evidence that these changes are associated with atrophy. The histological and gene expression changes occurring within the introitus after menopause may contribute to the constellation of symptoms that constitute the genitourinary syndrome of menopause.
Sections du résumé
BACKGROUND
BACKGROUND
The study aimed to determine the effect of menopausal status and hormone therapy on the introitus and labia majora at the levels of histology and gene expression.
METHODS
METHODS
Three cohorts of 10 women each (pre-menopause, post-menopause and post-menopause + hormone therapy) were selected based on the presentation of clinical atrophy and vaginal pH. Biopsies were obtained from the introitus (fourchette) and labia majora and processed for histology and gene expression analyses with microarrays. Other data collected included self-assessed symptoms, serum estradiol, testosterone, serum hormone binding globulin and the pH of the vagina and labia majora.
RESULTS
RESULTS
The introitus appears exquisitely sensitive to hormone status. Dramatic changes were observed in histology including a thinning of the epithelium in post-menopausal subjects with vaginal atrophy. Furthermore, there was differential expression of many genes that may contribute to tissue remodeling in the atrophic introitus. Levels of expression of genes associated with wound healing, angiogenesis, cell migration/locomotion, dermal structure, apoptosis, inflammation, epithelial cell differentiation, fatty acid, carbohydrate and steroid metabolism were significantly different in the cohort exhibiting atrophy of the introitus. While changes were also observed at the labia, that site was considerably less sensitive to hormone status. The gene expression changes observed at the introitus in this study were very similar to those reported previously in the atrophic vagina providing further evidence that these changes are associated with atrophy.
CONCLUSIONS
CONCLUSIONS
The histological and gene expression changes occurring within the introitus after menopause may contribute to the constellation of symptoms that constitute the genitourinary syndrome of menopause.
Identifiants
pubmed: 31803317
doi: 10.14740/jocmr4006
pmc: PMC6879024
doi:
Types de publication
Journal Article
Langues
eng
Pagination
745-759Informations de copyright
Copyright 2019, Binder et al.
Déclaration de conflit d'intérêts
MA Freedman and KB Sharma are consultants for The Procter & Gamble Company and received funding from Procter & Gamble for this study. RL Binder, MA Farage, Y Wang, C Combs, D Moore, JP Tiesman, CC Bascom, RJ Isfort and R Warren are current or former employees of Procter & Gamble.
Références
PLoS One. 2013 Jun 26;8(6):e67124
pubmed: 23840601
Cancer Res. 2000 Nov 15;60(22):6367-75
pubmed: 11103799
Maturitas. 2007 Dec 20;58(4):366-76
pubmed: 17997058
J Biol Chem. 2016 Jan 15;291(3):1103-14
pubmed: 26601954
Cell. 2007 May 4;129(3):523-36
pubmed: 17482546
J Biol Chem. 2015 Jun 26;290(26):16440-50
pubmed: 25979340
J Biol Chem. 2013 Nov 29;288(48):34304-24
pubmed: 24142692
Cell Rep. 2013 Feb 21;3(2):342-9
pubmed: 23403292
Nucleic Acids Res. 2009 Jan;37(1):1-13
pubmed: 19033363
Connect Tissue Res. 2006;47(4):177-89
pubmed: 16987749
Am J Med Sci. 1997 Oct;314(4):228-31
pubmed: 9332260
Nature. 2010 Mar 25;464(7288):504-12
pubmed: 20336132
J Gerontol A Biol Sci Med Sci. 2014 Jun;69 Suppl 1:S4-9
pubmed: 24833586
Elife. 2014 Jun 04;3:
pubmed: 24898756
Nat Genet. 2010 Oct;42(10):910-4
pubmed: 20871598
Eye (Lond). 2008 Jun;22(6):768-76
pubmed: 17491602
Am J Obstet Gynecol. 1972 May 1;113(1):98-103
pubmed: 5025003
Menopause. 2005 Nov-Dec;12(6):679-84
pubmed: 16278610
Menopause. 2013 Oct;20(10):1043-8
pubmed: 23571518
Mol Cell Endocrinol. 2014 Jul 5;392(1-2):115-24
pubmed: 24859604
Biol Reprod. 2015 Apr;92(4):99
pubmed: 25715794
J Endocrinol. 2011 Jun;209(3):261-72
pubmed: 21292729
EMBO Rep. 2014 Aug;15(8):903-10
pubmed: 24916387
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
BJOG. 2001 Aug;108(8):813-6
pubmed: 11510705
Genes Dev. 2006 Nov 15;20(22):3185-97
pubmed: 17114587
Clin Breast Cancer. 2015 Dec;15(6):527-535.e2
pubmed: 26283501
J Clin Endocrinol Metab. 2015 Aug;100(8):E1046-55
pubmed: 26066673
BMC Med Genomics. 2008 Jun 25;1:27
pubmed: 18578861
J Sex Med. 2013 Jul;10(7):1790-9
pubmed: 23679050
Maturitas. 1995 Jan;21(1):51-6
pubmed: 7731384
PLoS One. 2012;7(12):e50229
pubmed: 23226515
Obstet Gynecol. 1999 Nov;94(5 Pt 1):700-3
pubmed: 10546713
Mech Ageing Dev. 2009 Nov-Dec;130(11-12):793-800
pubmed: 19896963
J Biol Chem. 2009 Oct 9;284(41):28204-11
pubmed: 19696018
J Cell Sci. 2011 Dec 15;124(Pt 24):4172-83
pubmed: 22193962
Menopause. 2014 May;21(5):450-8
pubmed: 24080849
PLoS One. 2011;6(11):e26602
pubmed: 22073175
J Gen Intern Med. 2010 Jan;25(1):45-51
pubmed: 19908103
J Biol Chem. 2001 Jun 8;276(23):20397-406
pubmed: 11259407
Bioessays. 2002 Sep;24(9):811-20
pubmed: 12210517
J Steroid Biochem Mol Biol. 2014 Jul;142:121-31
pubmed: 24134950
Science. 2015 Dec 4;350(6265):1208-13
pubmed: 26785480
Br J Dermatol. 2010 Dec;163(6):1174-80
pubmed: 20738297
PeerJ. 2018 Dec 10;6:e6035
pubmed: 30581661
Nature. 2006 May 18;441(7091):362-5
pubmed: 16710422
J Drugs Dermatol. 2009 Jul;8(7 Suppl):s8-11
pubmed: 19623778
Science. 2015 Dec 4;350(6265):1191-3
pubmed: 26785476
Nat Immunol. 2010 Sep;11(9):785-97
pubmed: 20720586
Ageing Res Rev. 2015 Jan;19:53-64
pubmed: 25481406
Menopause. 2014 Oct;21(10):1063-8
pubmed: 25160739
Menopause. 2014 Apr;21(4):383-90
pubmed: 24080848
Biochim Biophys Acta. 2014 Mar;1841(3):409-15
pubmed: 23928127