Early Regenerative Modifications of Human Postmenopausal Atrophic Vaginal Mucosa Following Fractional CO2 Laser Treatment
BACKGROUND: Postmenopausal women experience undesired symptoms that adversely affect their quality of life. In the recent years, a specific 12 - week fractional CO2 laser treatment has been introduced, with highly significant relief of symptoms.
AIM: The aim of this paper is the identification of the early modifications of structural components of atrophic vaginal mucosa induced by laser irradiation, which is responsible for the restorative processes.
MATERIAL AND METHODS: We investigated by microscopical, ultrastructural and biochemical methods the modifications of the structural components of postmenopausal atrophic vaginal mucosa tissues after 1 hour following a single fractional laser CO2 application.
RESULTS: In one hour, the mucosal epithelium thickens, with the maturation of epithelial cells and desquamation at the epithelial surface. In the connective tissue, new papillae indenting the epithelium with newly formed vessels penetrating them, new thin fibrils of collagen III are also formed in a renewed turnover of components due to the increase of metalloproteinase - 2. Specific features of fibroblasts support stimulation of their activity responsible of the renewal of the extracellular matrix, with an increase of mechanical support as connective tissue and stimulation of growth and maturation to epithelium thanks to new vessels and related factors delivered.
CONCLUSION: We found the activation of regenerative mechanisms expressed both in the connective tissue - with the formation of new vessels, new papillae, and new collagen - and in the epithelium with the associated thickening and desquamation of cells at the mucosal surface.
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Salvatore S, Nappi RE, Zerbinati N, Calligaro A, Ferrero S, Origoni M, Candiani M, Leone Roberti Maggiore U. A 12-week treatment with fractional CO2 laser for vulvovaginal atrophy: a pilot study. Climacteric. 2014; 17(4):363-9. https://doi.org/10.3109/13697137.2014.899347 PMid:24605832
Perino A, Calligaro A, Forlani F, Tiberio C, Cucinella G, Svelato A, Saitta S, Calagna G. Vulvo-vaginal atrophy: a new treatment modality using thermo-ablative fractional CO2 laser. Maturitas. 2015; 80(3):296-301. https://doi.org/10.1016/j.maturitas.2014.12.006 PMid:25596815
Zerbinati N, Serati M, Origoni M, Candiani M, Iannitti T, Salvatore S, Marotta F, Calligaro A. Microscopic and ultrastructural modifications of postmenopausal atrophic vaginal mucosa after fractional carbon dioxide laser treatment. Lasers Med Sci. 2015; 30(1):429-36. https://doi.org/10.1007/s10103-014-1677-2 PMid:25410301
Sokol ER, Karram MM. An assessment of the safety and efficacy of a fractional CO2 laser system for the treatment of vulvovaginal atrophy. Menopause. 2016; 23:1102-7. https://doi.org/10.1097/GME.0000000000000700 PMid:27404032
Sokol ER, Karram MM. Use of a novel fractional CO2 laser for the treatment of genitourinary syndrome of menopause: 1-year outcomes. Menopause. 2017; 24:810-814. https://doi.org/10.1097/GME.0000000000000839 PMid:28169913
Behnia-Willison F, Sarraf S, Miller J, Mohamadi B, Care AS, Lam A, Willison N, Behnia L, Salvatore S. Safety and long-term efficacy of fractional CO2 laser treatment in women suffering from genitourinary syndrome of menopause. Eur J Obstet Gynecol Reprod Biol. 2017; 213:39-44. https://doi.org/10.1016/j.ejogrb.2017.03.036 PMid:28419911
Salvatore S, Nappi RE, Parma M, Chionna R, Lagona F, Zerbinati N, Ferrero S, Origoni M, Candiani M, Leone Roberti Maggiore U. Sexual function after fractional microablative COâ‚‚ laser in women with vulvovaginal atrophy. Climacteric. 2015; 18(2):219-25. https://doi.org/10.3109/13697137.2014.975197 PMid:25333211
Putchler H, Waldrop FS, Valentine LS. Polarization microscopic studies of connective tissue stained with picro-sirius red FBA. Beith Path. 1973; 150:174-187. https://doi.org/10.1016/S0005-8165(73)80016-2
Junqueira LC, Bignolas G, Brentani RR. Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections. Histochem J. 1979; 11:447-455. https://doi.org/10.1007/BF01002772 PMid:91593
Frohlich MW. Birefringent objects visualized by circular polarization microscopy. Stain Technol. 1986; 61:139-143.
Junqueira LCU, Cossermelli W, Brentani R . () Differential staining of collagens type I, II and III by sirius red and polarization microscopy. Arch. Histol. Jap. 1978; 41:267-274. https://doi.org/10.1679/aohc1950.41.267 PMid:82432
Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985; 150(1):76-85. https://doi.org/10.1016/0003-2697(85)90442-7
Salvatore S, Leone Roberti Maggiore U, Athanasiou S, Origoni M, Candiani M, Calligaro A, Zerbinati N. Histological study on the effects of microablative fractional CO2 laser on atrophic vaginal tissue: an ex vivo study. Menopause. 2015; 22(8):845-849. https://doi.org/10.1097/GME.0000000000000401 PMid:25608269
Pagano T, De Rosa P, Vallone R, Schettini F, Arpino G, De Placido S, Nazzaro G, Locci M, De Placido G. Fractional microablative CO2 laser for vulvovaginal atrophy in women treated with chemotherapy and/or hormonal therapy for breast cancer: a retrospective study. Menopause. 2016; 23:1108-13. https://doi.org/10.1097/GME.0000000000000672 PMid:27648595
Pieralli A, Fallani MG, Becorpi A, Bianchi C, Corioni S, Longinotti M, Tredici Z, Guaschino S. Fractional CO2 laser for vulvovaginal atrophy (VVA) dyspareunia relief in breast cancer survivors. Arch Gynecol Obstet. 2016; 294:841-6. https://doi.org/10.1007/s00404-016-4118-6 PMid:27170261
Aimes RT, Quigley JP. Matrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4-length fragments. J Biol Chem. 1995; 270:5872-6. https://doi.org/10.1074/jbc.270.11.5872 PMid:7890717
Lisboa RA, Andrade MV, Cunha-Melo JR. Zimography is an effective method for detection of matrix metalloproteinase 2 (MMP-2) activity in cultured human fibroblasts. Acta Cir Bras. 2013; 28:216-20. https://doi.org/10.1590/S0102-86502013000300010 PMid:23503864
Kleiner DE, Stetler-Stevenson WG. Quantitative zymography: detection of picogram quantities of gelatinases. Anal Biochem. 1994; 218:325-9. https://doi.org/10.1006/abio.1994.1186 PMid:8074288
de Jesus PD, Saeki SI, Tedesco AC. An ex vivo study of photobiostimulation in the treatment of skin pathologies. J Biophotonics. 2016; 9:1189-1198. https://doi.org/10.1002/jbio.201500288 PMid:26992152
Nowak KC, McCormack M, Koch RJ. The effect of superpulsed carbon dioxide laser energy on keloid and normal dermal fibroblast secretion of growth factors: a serum-free study. Plast Reconstr Surg. 2000; 105(6):2039â€“2048. https://doi.org/10.1097/00006534-200005000-00019 PMid:10839401
Manolis EN, Kaklamanos IG, Spanakis N, Filippou DK, Panagiotaropoulos T, Tsakris A, Siomos K. () Tissue concentration of transforming growth factor b1 and basic fibroblast growth factor in skin wounds created with a CO2 laser and scalpel: a comparative experimental study, using an animal model of skin resurfacing. Wound Repair Regen. 2007; 15:252â€“257. https://doi.org/10.1111/j.1524-475X.2007.00212.x PMid:17352758
Prignano F, Campolmi P, Bonan P, Ricceri F, Cannarozzo G, Troiano M, Lotti T. Fractional CO2 laser: a novel therapeutic device upon photobiomodulation of tissue remodeling and cytokine pathway of tissue repair. Dermatol Ther. 2009; 22(Suppl 1):S8â€“15. https://doi.org/10.1111/j.1529-8019.2009.01265.x PMid:19891690
Stephens DJ. Collagen secretion explained. Nature. 2012; 482:474-5. https://doi.org/10.1038/482474a PMid:22358830 PMCid:PMC3566552
Dayan D, Hiss Y, Hirshberg A, Bubis JJ, Wolman M. Are the polarization colors of picrosirius red-stained collagen determined only by the diameter of the fibers? Histochemistry. 1989; 93:27-29. https://doi.org/10.1007/BF00266843 PMid:2482274
Whittaker P, Kloner RA, Boughner DR, Pickering JG. Quantitative assessment of myocardial collagen with picrosirius red staining and circularly polarized light. Basic Research in Cardiology. 1994; 89:397-410. https://doi.org/10.1007/BF00788278 PMid:7535519
Whittaker P. Polarised light microscopy in biomedical research. Microsc Analysis. 1995; 33:13-15.
Borges LF, Gutierrez PS, Marana HRC, Taboga SR. Picrosirius-polarization staining method as an efficient histopathological tool for collagenolysis detection in vesical prolapse lesions. Micron. 2007; 38:580-583. https://doi.org/10.1016/j.micron.2006.10.005 PMid:17126553
Vidal BC, Mello ML, Pimentel ER. Polarization microscopy and microspectrophotometry of Sirius Red, Picrosirius and Chlorantine Fast Red aggregates and of their complexes with collagen. Histochem J. 1982; 14:857-78. https://doi.org/10.1007/BF01005229 PMid:6184330
Whittaker P, Boughner DR, Kloner RA. Analysis of healing after myocardial infarction using polarized light microscopy. Am J Pathol. 1989; 134:879-93. PMid:2705508 PMCid:PMC1879777
Rich L, Whittaker P. Collagen and picrosirius red staining: a polarized light assessment of fibrillar hue and spatial distribution. Braz. J. Morphol. Sci. 2005;22:97-104.
Mac Bride MB, Rhodes DJ, Shuster LT. Vulvovaginal atrophy. Mayo Clin Proc. 2010; 85(1):87-94. https://doi.org/10.4065/mcp.2009.0413 PMid:20042564 PMCid:PMC2800285
Athanasiou S, Pitsouni E, Antonopoulou S, Zacharakis D, Salvatore S, Falagas ME, Grigoriadis T. The effect of microablative fractional CO2 laser on vaginal flora of postmenopausal women. Climacteric. 2016; 19:512-518. https://doi.org/10.1080/13697137.2016.1212006 PMid:27558459
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