The pathogenesis of pelvic organ prolapse and pelvic floor dysfunction in women: Enzyme and genetic aspects

Kamoeva S.V.

doi:https://doi.org/

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Abstract:

The paper reviews the data available in the Russian and foreign literature on pelvic organ prolapse (POP) and pelvic floor dysfunction in women. It considers the role of enzyme and genetic aspects in the development of this disease. It is indicated that matrix proteins, FBLN-5 and LOXL1 in particular, are of importance in the formation of elastic fibers of connective tissue that is able to extend during labor and childbirth. The understanding of elastogenetic processes may give rise to targeted therapy for POP as an alternative to the only effective surgical treatment for pelvic floor dysfunction in women.

Keywords:

pelvic organ prolapse

matrix proteins

fibulin-5

elastogenesis

lysyl oxydase L1

Authors:

Kamoeva S.V.

Kafedra akusherstva i ginekologii lechebnogo fakul'teta Rossiĭskogo natsional'nogo issledovatel'skogo meditsinskogo universiteta im. N.I. Pirogova, Moskva

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References:

Adamyan L.V., Smol'nova T.Yu., Zairat'yants O.V., Yarotskaya E.L., Opalenov K.V. Morfofiziologicheskaya kharakteristika tkanevogo fenotipa u bol'nykh pri displazii soedinitel'noi tkani: sovremennye tekhnologii v diagnostike i lechenii ginekologicheskikh zabolevanii. Pod red. L.V. Adamyan. M 2007; 345-346.
Buyanova S.N., Savel'ev S.V., Petrova V.D., Shoibonov B.Zh., Murav'eva T.G., Fedorov A.A., Lukashenko S.Yu. Rol' displazii soedinitel'noi tkani v patogeneze prolapsa genitalii i nederzhaniya mochi. Ros vestn akush-gin. 2005; 5: 5:19-23.
Smol'nova T.Yu. Kliniko-patogeneticheskie aspekty opushcheniya i vypadeniya vnutrennikh polovykh organov i patologii struktur tazovogo kompleksa u zhenshchin pri displazii soedinitel'noi tkani: taktika vedeniya: Avtoref. dis. … d-ra med. nauk. M 2009; 57.
Cauwe B., Van den Steen P.E., Opdenakker G. The biochemical, biological, and pathological kaleidoscope of cell surface substrates processed by matrix metalloproteinase. Crit Rev Biochem Mol Biol 2007; 42: 3: 113-118.
Drewes P.G., Yanagisawa H., Starcher B., Hornstra I., Csiszar K., Marinis S.I., Keller P., Word R.A. Pelvic organ prolapse in fibulin-5 knockout mice (Pregnancy-induced changes in elastic fiber homeostasis in mouse vagina). Am J Pathol 2007; 170: 2: 578-589.
Duca L., Floquet N., Alix A.J.P., Haye B., Debelle L. Elastin as a matrikine. Crit Rev Oncol Hematol 2004; 49: 235-244.
Farrel S.A., Dempsey T., Geldenhuys L. Histologic examination of "fascia”used in colporrhaphy. Obstet Ginaec 2001; 5: 98: Pt 1: 794-798.
Fisher G.J., Choi H.C., Bata-Csorgo Z., Shao Y., Datta S., Wang Z.Q., Kang S., Voorhees J.J. Ultraviolet irradiation increases matrix metalloproteinase-8 protein in human skin in vivo. J Invest Dermatol 2001; 117: 219-226.
Gabriel B., Watermann D., Hancke K., Gitsch G., Werner M., Tempfer C., Hausen A. Increased expression of matrix metalloproteinase 2 in uterosacral ligaments is associated with pelvic organ prolapse. Int Urogynecol J Pelvic Floor Dysfunct 2006; 17: 478-482.
Hundley A.F., Yuan L., Visco A.G. Skeletal muscle heavy-chain polypeptide 3 and myosin binding protein H in the pubococcygeus muscle in patient with and without pelvic organ prolapse. Am J Obstet Gynec 2006; 194: 5: 1404-1410.
Ireland D.C., Bord S., Beavan S.R., Compston J.E. J Cell Biochem 2004; 9L: 3: 594-601.
Jepsen K.J., Wu F., Peragallo J.H., Paul J., Roberts L., Ezura Y., Oldberg A., Birk D.E., Chakravarti S. A syndrome of joint laxity and impaired tendon integrity in lumican- and fibromodulin-deficient mice. J Biol Chem 2002; 277: 38: 35532-35540.
Kielty C.M., Sherratt M.J., Shuttleworth C.A. Elastic fibres. J Cell Sci 2002; 115: 2817-2828.
Kostka G., Giltay R., Bloch W., Addicks K., Timpl R., Fassler R., Chu M.L. Perinatal lethality and endothelial cell abnormalities in several vessel compartments of fibulin-1-deficient mice. Mol Cell Biol 2001; 21: 7025-7034.
Lenhardt R., Hopf H.W., Maarker E., Akça O., Kurz A., Scheuenstuhl H., Sessler D.I. Perioperative collagen deposition in elderly and young men and women. Arch Surg 2000; 135: L-P: 71-74.
Liu G., Daneshgari F., Li M., Lin D.L., Lee U., Li T., Damaser M.S. Bladder and urethral function in pelvic organ prolapsed lysyl oxidase like-1 knockout mice. BJU Int 2007; 100: 414-418.
Liu X., Zhao Y., Gao J., Pawlyk B., Starcher B., Spencer J.A., Yanagisawa H., Zuo J., Li T. Elastic fiber homeostasis requires lysyl oxidase-like 1 protein. 2004; 36: 2: 178-182.
Marinis S., Boreham M., Wai C., Corton M., Nihira M., Schaffer J., Word R. Activation of immune cells in vaginal muscularis of women with pelvic organ prolapse. J Pelvic Med Surg 2003; 9: 5.
McLaughlin P.J., Chen Q., Horiguchi M., Starcher B.C., Stanton J.B., Broekelmann T.J., Marmorstein A.D., McKay B., Mecham R., Nakamura T., Marmorstein L.Y. Targeted disruption of fibulin-4 abolishes elastogenesis and causes perinatal lethality in mice. Mol Cell Biol 2006; 26: 1700-1709.
McLaughlin P.J., Bakall B., Choi J., Liu Z., Sasaki T., Davis E.C., Marmorstein A.D., Marmorstein L.Y. Lack of fibulin-3 causes early aging and herniation, but not macular degeneration in mice. Hum Mol Genet 2007; 16: 3059-3070.
Nguyen A.D., Itoh S., Jeney V., Yanagisawa H., Fujimoto M., Ushio-Fukai M., Fukai T. Fibulin-5 is a novel binding protein for extracellular superoxide dismutase. Circ Res 2004; 95: 1067-1074.
Parks W., Secrist H., Wu L., Mecham R. Developmental regulation of tropoelastin isoforms. J Biol Chem 1988; 263: 4416-4423.
Phillips C.H., Anthony F., Benyon C., Monga A.K. Collagen metabolism in the utero-sacral ligaments and vaginal skin of women with uterine prolapse. BJOG 2006; 113: 39-46.
Rauch F., Georg M., Stabrey A. Collagen markers deoxypyridinoline and hydroxylysine glycosides: Pediatric reference data and use for growth prediction in growth hormone deficient children. Clin Chem 2002; 48: 315-322.
Rahn D.D., Acevedo J.F., Word R.A. Effect of vaginal distention on elastic fiber synthesis and matrix degradation in the vaginal wall: potential role in the pathogenesis of pelvic organ prolapse. Am J Phisiol Regul Integr Comp Phisiol 2008; 295: 4: 1351-1358.
Rahn D.D., Ruff M.D., Brown S., Tibbals H.F., Word R.A. Biomechanical properties of the mouse vagina: changes seen in pregnancy and with elastinopathy. Am J Obstet Gynecol 2008; 198: 590e1-590e6.
Saarela T., Risteli J., Kauppila A., Koivisto M. Effect of short-term antenatal dexamethasone administration on type I collagen synthesis and degradation in preterm infants at birth. Acta Paediatr 2001; 90: 8: 921-925.
Swift S., Woodman P., O'Boyle A., Kahn M., Valley M., Bland D., Wang W., Schaffer J. Pelvic Organ Support Study (POSST): The distribution, clinical definition, and epidemiologic condition of pelvic organ support defects. Am J Obstet Gynec 2005; 192: 795-806.
Takacs P., Nassiri M., Viciana A., Candiotti K., Fornoni A., Medina C.A. Fibulin-5 expression is decreased in women with anterior vaginal wall prolapsed. International urogynecology journal and pelvic floor dysfunction 2009; 20: 2: 207-211.
de Vega S., Iwamoto T., Nakamura T., Hozumi K., McKnight D.A., Fisher L.W., Fukumoto S., Yamada Y. TM14 is a new member of the fibulin family (fibulin-7) that interacts with extracellular matrix molecules and is active for cell binding. J Biol Chem 2007; 282: 30 878 -30 888.
Wieslander C.K., Marinis S.I., Drewes P.G., Keller P.W., Acevedo J.F., Word R.A. Regulation of elastolytic proteases in the mouse vagina during pregnancy, parturition, and puerperium. Biol Reprod 2008; 78: 521-528.
Wieslander C.K., Rahn D.D., McIntire D.D., Acevedo J.F., Drewes P.G., Yanagisawa H., Word R.A. Quantification of pelvic organ prolapsed in mice: vaginal protease activity increased MOPQ scores in fibulin 5 knockout mice. Biol Reprod 2009; 80: 3: 407-414.
Word R.A., Schaffer J.I., McIntire D.D., Woodman P., O'Boyle A., Kahn M., Valley M., Bland D., Swift S.E. Smoking is a risk factor for pelvic organ prolapse. J Pelv Med Surg 2005; 11: 16.
Zacchigna L., Vecchione C., Notte A., Cordenonsi M., Dupont S., Maretto S., Cifelli G., Ferrari A., Maffei A., Fabbro C. Emilin1 links TGF-beta maturation to blood pressure homeostasis. Cell 2006; 124: 5: 929-942.
Zhao L., Samuel C.S., Tregear G.W., Beck F., Wintour E.M. Collagen studies in late pregnant relaxin null mice. Biol Reprod 2000; 63: 697-703.
Zhao S., Fields P.A., Sherwood O.D. Evidence that relaxin inhibits apoptosis in the cervix and the vagina during the second half of pregnancy in the rat. Endocrinology 2001; 142: 2221-2229.
Zhao Y.-G., Xiao A.-Z., Cao X.-M., Zhu C. Expression of matrix metalloproteinase -2, -9 and tissue inhibitors of metalloproteinase -1, -2, -3 mRNAs in rat uterus during early pregnancy. Molecular Reproduction and Development 2002; 62: 149-158.
Zong W., Zyczynski H.M., Meyn L.A., Gordy S.C., Moalli P.A. Regulation of MMP-1 by sexsteroid hormones in fibroblasts derived from the female pelvic floor. Am J Obstet Gynecol 2007; 196: 349: e341-311, 39-46.