Analysis of differential expression of genes of structural and regulatory proteins of connective tissue as factors associated with the vaginal prolapse
DOI:
https://doi.org/10.18370/2309-4117.2023.69.24-29Keywords:
pelvic organ prolapse, COLIA1, fibronectin, elastin, TGF-β1, LOX, stigmas of undifferentiated connective tissue dysplasiaAbstract
The article presents data on the differential expression of genes of structural and regulatory proteins of connective tissue (COLIA1, fibronectin, elastin, TGF-β1, LOX) in women with pelvic organ prolapse and stigmas of undifferentiated connective tissue dysplasia (UCTD) compared to patients with prolapse but without UCTD stigmas.
Research objectives: analysis of the prognostic significance of differential expression of structural and regulatory genes of connective tissue proteins COLIA1, fibronectin, elastin, TGF-β1, LOX as factors associated with the vaginal prolapse among Ukrainian women.
Materials and methods. Vaginal tissue samples were taken from 18 patients at the menopausal age with vaginal prolapse III, IV degree, which required surgical correction during vaginal hysterectomy and/or plastic surgery of vaginal walls. The main group included 11 patients with clinical and anamnestic UCTD stigmas, the comparison group included 7 women without it. Gene expression analysis of structural and regulatory proteins of the extracellular matrix of connective tissue was performed using real-time quantitative polymerase chain reaction. The relative number of transcripts of the studied genes was normalized by the expression level of the GAPDH gene. The data were calculated using the 2–ΔΔCt method.
Results. There was decrease in gene expression of the main structural proteins of the extracellular matrix of the connective tissue: COLIA1 (t=-1.7; p=0.044), fibronectin (t=1.66; p=0.047), elastin (t=-1.75, p=0,04), gene of the regulatory protein LOX (t=-1.8, p=0.035) and no statistically significant difference in the TGF-β1 gene in patients with pelvic organ prolapse and clinical and anamnestic UCTD stigmas.
Conclusions. Statistically significant lower expression of the genes of the main structural proteins of the extracellular matrix of the connective tissue and the gene of the regulatory protein LOX in patients with pelvic organ prolapse and clinical and anamnestic UCTD stigmas is evidence of the importance of genetically determined pathological remodeling of the connective tissue in the etiology of genital prolapse.
References
- Hendrix, S.L., Clark, A., Nygaard, et al. Pelvic organ prolapse in the Women’s Health Initiative: gravity and gravidity. Am J. Obstet Gynecol. 2002; 186(6): 1160–66.
- Swift, S., Woodman, P., O’Boyle, A., et al. Pelvic Organ Support Study (POSST): the distribution, clinical definition, and epidemiologic condition of pelvic organ support defects. Am J. Obstet Gynecol. 2005; 192(3): 795–806.
- Weintraub, A.Y. Narrative review of the epidemiology, diagnosis and pathophysiology of pelvic organ prolapse / A.Y. Weintraub, H. Glinter, N. Marcus-Braun // Int. Braz. J. Urol. – 2020. – Vol. 46 (1). – Р. 5–14.
- Persson P., Brynhildsen J., Kjolhede P. Hysterectomy Multicentre Study Group in South-East Sweden. Pelvic organ prolapse after subtotal and total hysterectomy: a long-term follow-up of an open randomised controlled multicentre study. BJOG. 2013 Nov; 120(12): 1556-65. doi: 10.1111/1471-0528.12399. Epub 2013 Aug 20. PMID: 24034602.
- Dieter, A.A. Pelvic Organ Prolapse: Controversies in Surgical Treatment. Obstet Gynecol Clin North Am. 2021 Sep; 48(3): 437–448. doi: 10.1016/j.ogc.2021.05.001. PMID: 34416930.
- Meriwether, K.V., Antosh, D.D., Olivera, C.K., Kim-Fine, S. “Uterine preservation vs hysterectomy in pelvic organ prolapse surgery: a systematic review with metaanalysis and clinical practice guidelines.” Am J Obstet Gynecol 219.2 (2018): 129–46.
- Wu, J.M., Matthews, C.A., Conover, M.M. Lifetime risk of stress urinary incontinence or pelvic organ prolapse surgery. Obstet Gynecol. 2014; 123(6): 1201–06.
- Gillor, M. Demographic risk factors for pelvic organ prolapse: Do smoking, asthma, heavy lifting or family history matter? / M. Gillor, P. Saens, H.P. Dietz // Eur. J. Obstet. Gynecol. Reprod. Biol. – 2021. – No. 261. – Р. 25–28.
- Association between delivery mode and pelvic organ prolapse: A meta-analysis of observational studies / B. Leng, Y. Zhou, S. Du [et al.] // Eur. J. Obstet. Gynecol. Reprod. Biol. – 2019. – No. 235. – Р. 19–25.
- Obesity and pelvic organ prolapse / U.J. Lee, M. H. Kerkhof, S.A. van Leijsen, J.P. Heesakkers // Curr. Opin. Urol. – 2017. – No. 27 (5). – Р. 428–434. Advancing our understanding of genetic risk factors and potential personalized strategies for pelvic organ prolapse / N. Pujol-Gualdo, K. Lall, M. Lepamets [et al.] // Nat Commun. – 2022. – No. 13 (1).
- Vergeldt, T.F., Weemhoff, M., IntHout, J., Kluivers, K.B. Risk factors for pelvic organ prolapse and its recurrence: a systematic review. Int Urogynecol J. 2015; 26(11): 1559–73.
- Lince, S.L., van Kempen, L.C., Vierhout M.E., Kluivers, K.B. A systematic review of clinical studies on hereditary factors in pelvic organ prolapse. Int Urogynecol J. 2012; 23(10): 1327–36.
- Buchsbaum, G.M., Duecy, E.E. Incontinence and pelvic organ prolapse in parous/ nulliparous pairs of identical twins. Neurourol Urodyn. 2008; 27(6): 496–8.
- Samimi, P., Jones, S.H., Giri, A. Family history and pelvic organ prolapse: a systematic review and meta-analysis. Int Urogynecol J. ePublication ahead of print. 2020. https://doi. org/10.1007/s00192-020-04559-z
- 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 e191–124.
- Allen-Brady, K., Cannon-Albright, L., Farnham, J.M., et al. Identification of six loci associated with pelvic organ prolapse using genome-wide association analysis. Obstet Gynecol. 2011; 118(6): 1345–53.
- Murphy-Ryan, M., Psychogios, A., Lindor, N. Hereditary disorders of connective tissue: a guide to the emerging differential diagnosis. Genetics in Medicine. 2010; 12(6): 344–54. doi:10.1097/ GIM.0b013e3181e074f0.
- Aringer, M., Steiner, G., Smolen, J.S. Does mixed connective tissue disease exist? Yes. Rheumatic disease clinics of North America. 2005; 31(3): 411–20. doi: 10.1016/j.rdc.2005.04.007
- Kluivers K.B., Lince S.L., Ruiz-Zapata A.M., et al. Molecular Landscape of Pelvic Organ Prolapse Provides Insights into Disease Etiology. Int J. Mol Sci. 2023 Mar 23; 24(7): 6087. doi: 10.3390/ijms24076087. PMID: 37047060; PMCID: PMC10094264
- Zhao, B.H., Zhou, J.H. Decreased expression of elastin, fibulin-5 and lysyl oxidase-like 1 in the uterosacral ligaments of postmenopausal women with pelvic organ prolapse. J Obstet Gynaecol Res. 2012 Jun; 38(6): 925–31. doi: 10.1111/j.1447-0756.2011.01814.x. Epub 2012 Apr 9. PMID: 22487196.
- Tremollieres, F. Tissu conjonctif de soutien et genese des prolapsus [Connective tissue and prolapse genesis]. Gynecol Obstet Fertil. 2010 Jun; 38(6): 388–93. French. doi: 10.1016/j.gyobfe.2010.04.005. Epub 2010 Jun 4. PMID: 20576547.
- Kufaishi, H., Alarab, M., Drutz H. et al. Comparative Characterization of Vaginal Cells Derived From Premenopausal Women With and Without Severe Pelvic Organ Prolapse. Reprod Sci. 2016 Jul; 23(7): 931–43. doi: 10.1177/1933719115625840. Epub 2016 Jan 13. PMID: 26763525.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 О.М. Прощенко, Д.О. Говсєєв, І.Б. Венцківська
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.