Markers of connective tissue remodeling in genital prolapse


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Abstract

Objective - to expand the conception of molecular and biochemical changes in genital prolapse (GP) based on the study of morphological and immunohistochemical features in connective tissue structures of the ligamentous apparatus of the pelvic floor and their dependence on genetic polymorphisms MMP/TIMP. Materials and methods. The study involved 178 women aged 35 to 65, 134 of them with GP relapses (after hysterectomy by vaginal access because of a total and partial uterus and vaginal walls prolapse). Patients were randomized into the following groups: 1 - with manifestations of undifferentiated connective tissue dysplasia - CTD (11.7 points on average; n=86); 2 - with no CTD signs (n=48). Control group 3 consisted of healthy women without any GP signs (among 15 patients abdominal hysterectomy was performed in connection with uterus hyperplastic processes); n=44. Used. Morphological method of studies, immunohistochemical (to assess tissue biopsies of sacrum-uterine and round uterine ligaments), the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs), genotyping by polymerase chain reaction of MMP/TIMP polymorphisms. Results. The morphological study of women’s ligamentous apparatus in cases with GP revealed significant fibrosis, coarser collagen septa among bundles of smooth muscle fibers and degenerative changes in individual smooth muscle cells. The group with GP and CTD features showed diffuse atrophy, hyaline or mucinous degeneration of smooth muscle tissue and evident edema of extracellular matrix in 65% of samples. Pathobiochemical disorders in cases of pelvic descencia were determined by an imbalance in collagen type I and III content, with the predominance of the latter, less durable; a decrease in elastin levels and its considerable fragmentation. The greatest expression of tissue degradation was observed among women with GP and CTD manifestations on account of increased MMP-1 and -2 levels; TIMP-1 content was lowest in the group. Associations with GP development have been established among women with CTD signs for genetic polymorphisms: rs3918242 СT gene MMP9 (0.54) (p=0.007; OR 3.2; 95% CI 1.3-7.6), rs17576 AG gene MMP9 (0.62 vs. 0.32, p=0.01; OR 2.9; 95% CI 1.2-7.0); rs3025058 5A6A gene MMP3 (0.52 vs. 0.45, p=0.009; OR 3.7; 95% CI 1.3-10.1); rs2285053 (rs2285052) CT gene MMP2 (0.44 vs. 0.27, p=0.007; OR 3.2; 95% CI 1.3-7.5). Statistical significance for the groups was preserved after the correction for multiple comparisons. Conclusion. The data obtained reveal pathogenetic aspects of genital prolapse - the prevalence of extracellular matrix degradation in a dysplastic morphogenesis. Genetic predictors of pelvic floor remodeling including the formation of its insolvency were established, allowing to extend the range of diagnostic possibilities of the disease progression at early stages or detection the risk of recurrence after surgical treatment. Personification of high-risk groups conducting provides for the exclusion or modification of all the factors predisposing to the development of the disease and performing timely treatment and preventive measures.

About the authors

M L Khanzadian

People’s Friendship University of Russia

Email: khmala@rambler.ru
канд. мед. наук, доц. каф. акушерства, гинекологии и репродуктивной медицины ФПК МР ФГАОУ ВО РУДН 117198, Russian Federation, Moscow, ul. Miklukho-Maklaya, d. 6

V E Radzinskii

People’s Friendship University of Russia

Email: radzinsky@mail.ru
д-р мед. наук, проф., зав. каф. акушерства и гинекологии с курсом перинатологии ФГАОУ ВО РУДН 117198, Russian Federation, Moscow, ul. Miklukho-Maklaya, d. 6

T A Demura

I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation

Email: demura-t@yandex.ru
д-р мед. наук, проф. каф. патологической анатомии им. акад. А.И.Струкова ГБОУ ВПО Первый МГМУ им. И.М.Сеченова 119991, Russian Federation, Moscow, ul. Trubetskaya, d. 8, str. 2

A E Donnikov

Company DNA-Technology LLC

канд. мед. наук, рук. медицинского отдела ООО «НПФ ДНК-Технология» 117587, Russian Federation, Moscow, Varshavskoe sh., d. 125zh, korp. 6

References

  1. Радзинский В.Е. Перинеология. М.: РУДН, 2010.
  2. Budatha M, Roshanravan S, Zheng Q et al. Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans. J Clin Invest 2011; 121 (5): 2048-59.
  3. Zong W, Stein S.E, Starcher B et al. Alteration of vaginal elastin metabolism in women with pelvic organ prolapse. Obstet Gynecol 2010; 115 (5): 953-61.
  4. De Landsheere L, Munaut C, Nusgens B et al. Histology of the vaginal wall in women with pelvic organ prolapse: a literature review. Int Urogynecol J 2013; 24 (12): 2011-20.
  5. Slieker-ten Hove M.C, Pool-Goudzwaard A.L, Eijkemans M.J et al. Prediction model and prognostic index to estimate clinically relevant pelvic organ prolapse in a general female population. Int Urogynecol J Pelvic Floor Dysfunct 2009; 20 (9): 1013-21.
  6. Yu H.Y, Yang X, Li G.H. Prospective study of the impact on lower urinary tract symptoms after pelvic organ prolapse surgery. Zhonghua Fu Chan Ke Za Zhi 2011; 46 (8): 570-3.
  7. Malemud C.J. Matrix metalloproteinases (MMPs) in health and disease: an overview. Front Biosci 2006; 11: 1696-701.
  8. Кадурина Т.И. Наследственные коллагенопатии (клиника, диагностика, лечение и диспансеризация). СПб.: Невский диалект, 2000.
  9. Chen B, Yeh J. Alterations in connective tissue metabolism in stress incontinence and prolapse. J Urol 2011; 186 (5): 1768-72.
  10. Кадурина Т.И. Дисплазия соединительной ткани. Руководство для врачей. СПб: ЭЛБИ, 2009.
  11. Yucel N, Usta A, Guzin K et al. Immunohistochemical analysis of connective tissue in patients with pelvic organ prolapse. J Mol Histol 2013; 44 (1): 97-102.
  12. Gabriel B, Watermann D, Hancke K et al. Increased expression of matrix metalloproteinase 2 in uterosacral ligaments is associated with pelvic organ prolapse. Int Urogynecol J Pelvic Floor Dysfunct 2006; 17 (5): 478-82.
  13. Abramowitch S.D, Feola A, Jallah Z et al. Tissue mechanics, animal models, and pelvic organ prolapse: a review. Eur J Obstet Gynecol Reprod Biol 2009; 144 (Suppl. 1): S146-58.
  14. Karam J.A, Vazquez D.V, Lin V.K et al. Elastin expression and elastic fibre width in the anterior vaginal wall of postmenopausal women with and without prolapse. BJU Int 2007; 100 (2): 346-50.
  15. Vulic M, Strinic T, Tomic S et al. Difference in expression of collagen type I and matrix metalloproteinase-1 in uterosacral ligaments of women with and without pelvic organ prolapse. Eur J Obstet Gynecol Reprod Biol 2011; 155 (2): 225-8.
  16. Chen L, Wang T, Liu L et al. Matrix metalloproteinase-9 -1562C/T promoter polymorphism confers risk for COPD: a meta - analysis. PLoS One 2013; 8(3): e60523.
  17. Li M, Shi J, Fu L et al. Genetic polymorphism of MMP family and coronary disease susceptibility: a meta - analysis. Gene 2012; 495 (1): 36-41.
  18. Cartwright R, Kirby A.C, Tikkinen K.A et al. Systematic review and metaanalysis of genetic association studies of urinary symptoms and prolapse in women. Am J Obstet Gynecol 2015; 212 (2): 199.e1-24.
  19. Chen H.Y, Lin W.Y, Chen Y.H et al. Matrix metalloproteinase-9 polymorphism and risk of pelvic organ prolapse in Taiwanese women. Eur J Obstet Gynecol Reprod Biol 2010; 149 (2): 222-4.
  20. Wu J.M, Visco A.G, Grass E.A et al. Matrix metalloproteinase-9 genetic polymorphisms and the risk for advanced pelvic organ prolapse. Obstet Gynecol 2012; 120 (3): 587-93.

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