Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
권호 표지
DOI QR코드

DOI QR Code

Patterns of proliferation and fibrosis in a rat model of endometriosis following administration of Allium cepa

  • Hakan Kula (Department of Obstetrics and Gynecology, Dokuz Eylul University) ;
  • Orkun Ilgen (Department of Obstetrics and Gynecology, Dokuz Eylul University) ;
  • Sefa Kurt (Department of Obstetrics and Gynecology, Dokuz Eylul University) ;
  • Filiz Yilmaz (Department of Histology and Embryology, Hitit University)
  • Received : 2023.06.08
  • Accepted : 2023.11.14
  • Published : 2024.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objective: Endometriosis is a common gynecological disease among reproductive-age women. Numerous hypotheses exist regarding the pathogenesis of endometriosis. In Turkey, the consumption of Allium cepa (commonly known as the "onion cure") is a popular treatment employed to alleviate a variety of gynecological disorders. Methods: In this study, our objective was to assess the therapeutic mechanisms of the onion bulb A. cepa using an autologous endometriosis model in Sprague-Dawley rats. Previous research has shown that A. cepa possesses anti-inflammatory, antioxidant, and antiapoptotic properties. We evaluated the pathological condition of endometriotic implants by employing hematoxylin-eosin staining and Ki67 immunohistochemistry analysis. Transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) have been identified as profibrotic markers that are highly overexpressed in endometriotic tissues relative to eutopic endometrial tissue. Furthermore, TGF-β1 influences the differentiation and progression of endometriosis. To quantify profibrotic activity, we measured TGF-β1 and α-SMA using the immunosorbent assay method. Results: Lower histologic evaluation scores for endometriotic implants were observed in the group receiving high-dose A. cepa relative to the other groups. Ki67 expression was reduced following the high-dose A. cepa regimen, which consisted of 30% A. cepa and 70% normal feed. However, no statistically significant differences in TGF-β1 or α-SMA levels were observed among the groups (p=0.7 and p=0.778, respectively). Conclusion: The findings suggest that A. cepa could serve as a therapeutic agent in endometriosis treatment, as evidenced by the reduction in proliferative potential. Nevertheless, A. cepa was not associated with significantly lower levels of endometriosis-associated TGF-β1 or α-SMA.

Keywords

References

  1. Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet 2021;397:839-52.  https://doi.org/10.1016/S0140-6736(21)00389-5
  2. Carson SA, Kallen AN. Diagnosis and management of infertility: a review. JAMA 2021;326:65-76.  https://doi.org/10.1001/jama.2021.4788
  3. Dun EC, Kho KA, Morozov VV, Kearney S, Zurawin JL, Nezhat CH. Endometriosis in adolescents. In: Nezhat CH, editor. Endometriosis in adolescents. Springer; 2020. p. 129-41. 
  4. Samimi M, Pourhanifeh MH, Mehdizadehkashi A, Eftekhar T, Asemi Z. The role of inflammation, oxidative stress, angiogenesis, and apoptosis in the pathophysiology of endometriosis: basic science and new insights based on gene expression. J Cell Physiol 2019;234:19384-92.  https://doi.org/10.1002/jcp.28666
  5. Burney RO. Fibrosis as a molecular hallmark of endometriosis pathophysiology. Fertil Steril 2022;118:203-4.  https://doi.org/10.1016/j.fertnstert.2022.05.004
  6. Malutan AM, Drugan T, Costin N, Ciortea R, Bucuri C, Rada MP, et al. Pro-inflammatory cytokines for evaluation of inflammatory status in endometriosis. Cent Eur J Immunol 2015;40:96-102.  https://doi.org/10.5114/ceji.2015.50840
  7. Matsuzaki S, Darcha C, Maleysson E, Canis M, Mage G. Impaired down-regulation of E-cadherin and beta-catenin protein expression in endometrial epithelial cells in the mid-secretory endometrium of infertile patients with endometriosis. J Clin Endocrinol Metab 2010;95:3437-45.  https://doi.org/10.1210/jc.2009-2713
  8. Vigano P, Candiani M, Monno A, Giacomini E, Vercellini P, Somigliana E. Time to redefine endometriosis including its pro-fibrotic nature. Hum Reprod 2018;33:347-52.  https://doi.org/10.1093/humrep/dex354
  9. Meligy FY, Elgamal DA, Abdelzaher LA, Khashbah MY, El-Mokhtar MA, Sayed AA, et al. Adipose tissue-derived mesenchymal stem cells reduce endometriosis cellular proliferation through their anti-inflammatory effects. Clin Exp Reprod Med 2021;48:322-36.  https://doi.org/10.5653/cerm.2021.04357
  10. Yalcin SE, Ocal I, Yalcin Y, Selim HS, Caltekin MD, Aydogmus H, et al. Evaluation of the Ki-67 proliferation index and urocortin expression in women with ovarian endometriomas. Eurasian J Med 2017;49:107-12.  https://doi.org/10.5152/eurasianjmed.2017.17070
  11. Galavi A, Hosseinzadeh H, Razavi BM. The effects of Allium cepa L. (onion) and its active constituents on metabolic syndrome: a review. Iran J Basic Med Sci 2021;24:3-16. 
  12. Lagana AS, Sofo V, Salmeri FM, Palmara VI, Triolo O, Terzic MM, et al. Oxidative stress during ovarian torsion in pediatric and adolescent patients: changing the perspective of the disease. Int J Fertil Steril 2016;9:416-23. 
  13. Marefati N, Ghorani V, Shakeri F, Boskabady M, Kianian F, Rezaee R, et al. A review of anti-inflammatory, antioxidant, and immunomodulatory effects of Allium cepa and its main constituents. Pharm Biol 2021;59:287-302.  https://doi.org/10.1080/13880209.2021.1874028
  14. Kula H, Ilgen O, Kurt S, Yilmaz F. Effects of Allium cepa on ovarian torsion-detorsion injury in a rat model. Turk J Obstet Gynecol 2023;20:137-41.  https://doi.org/10.4274/tjod.galenos.2023.41763
  15. Park S, Lim W, Bazer FW, Whang KY, Song G. Quercetin inhibits proliferation of endometriosis regulating cyclin D1 and its target microRNAs in vitro and in vivo. J Nutr Biochem 2019;63:87-100.  https://doi.org/10.1016/j.jnutbio.2018.09.024
  16. Kocadal NC, Attar R, Yildirim G, Ficicioglu C, Ozkan F, Yilmaz B, et al. Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model. J Turk Ger Gynecol Assoc 2013;14:81-6.  https://doi.org/10.5152/jtgga.2013.53179
  17. Jouhari S, Mohammadzadeh A, Soltanghoraee H, Mohammadi Z, Khazali S, Mirzadegan E, et al. Effects of silymarin, cabergoline and letrozole on rat model of endometriosis. Taiwan J Obstet Gynecol 2018;57:830-5.  https://doi.org/10.1016/j.tjog.2018.10.011
  18. Keenan JA, Williams-Boyce PK, Massey PJ, Chen TT, Caudle MR, Bukovsky A. Regression of endometrial explants in a rat model of endometriosis treated with the immune modulators loxoribine and levamisole. Fertil Steril 1999;72:135-41.  https://doi.org/10.1016/S0015-0282(99)00157-0
  19. Symons LK, Miller JE, Tyryshkin K, Monsanto SP, Marks RM, Lingegowda H, et al. Neutrophil recruitment and function in endometriosis patients and a syngeneic murine model. FASEB J 2020;34:1558-75.  https://doi.org/10.1096/fj.201902272R
  20. Nasu K, Nishida M, Kawano Y, Tsuno A, Abe W, Yuge A, et al. Aberrant expression of apoptosis-related molecules in endometriosis: a possible mechanism underlying the pathogenesis of endometriosis. Reprod Sci 2011;18:206-18.  https://doi.org/10.1177/1933719110392059
  21. Hung SW, Zhang R, Tan Z, Chung JP, Zhang T, Wang CC. Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: a review. Med Res Rev 2021;41:2489-564.  https://doi.org/10.1002/med.21802
  22. Onalan G, Tohma YA, Zeyneloglu HB. Effect of etanercept on the success of assisted reproductive technology in patients with endometrioma. Gynecol Obstet Invest 2018;83:358-64.  https://doi.org/10.1159/000484895
  23. Cordaro M, Trovato Salinaro A, Siracusa R, D'Amico R, Impellizzeri D, Scuto M, et al. Hidrox and endometriosis: biochemical evaluation of oxidative stress and pain. Antioxidants (Basel) 2021;10:720. 
  24. Gordts S, Koninckx P, Brosens I. Pathogenesis of deep endometriosis. Fertil Steril 2017;108:872-85.  https://doi.org/10.1016/j.fertnstert.2017.08.036
  25. Ramalingam M, Kim H, Lee Y, Lee YI. Phytochemical and pharmacological role of liquiritigenin and isoliquiritigenin from Radix Glycyrrhizae in human health and disease models. Front Aging Neurosci 2018;10:348. 
  26. Hsu YW, Chen HY, Chiang YF, Chang LC, Lin PH, Hsia SM. The effects of isoliquiritigenin on endometriosis in vivo and in vitro study. Phytomedicine 2020;77:153214. 
  27. Dela Cruz C, Reis FM. The role of TGFβ superfamily members in the pathophysiology of endometriosis. Gynecol Endocrinol 2015;31:511-5.  https://doi.org/10.3109/09513590.2015.1018166
  28. Zhang Z, Suo L, Chen Y, Zhu L, Wan G, Han X. Endometriotic peritoneal fluid promotes myofibroblast differentiation of endometrial mesenchymal stem cells. Stem Cells Int 2019;2019:6183796. 
  29. Siracusa R, D'Amico R, Cordaro M, Peritore AF, Genovese T, Gugliandolo E, et al. The methyl ester of 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid reduces endometrial lesions development by modulating the NFkB and Nrf2 pathways. Int J Mol Sci 2021;22:3991. 
  30. Huang Q, Liu X, Guo SW. Higher fibrotic content of endometriotic lesions is associated with diminished prostaglandin E2 signaling. Reprod Med Biol 2021;21:e12423. 
  31. Oyewusi AJ, Oridupa OA, Saba AB, Oyewusi IK, Olukunle JO. Anti-inflammatory and analgesic effects of methanol extract of red cultivar Allium cepa bulbs in rats and mice. J Basic Clin Physiol Pharmacol 2021;32:1087-92.  https://doi.org/10.1515/jbcpp-2020-0080
  32. Istrate-Ofiteru AM, Pirici D, Niculescu M, Berceanu C, Berceanu S, Voicu NL, et al. Clinical, morphological and immunohistochemical survey in different types of endometriosis. Rom J Morphol Embryol 2018;59:1133-53. 
  33. Bratila E, Bratila CP, Comandasu DE, Bausic V, Vladescu CT, Mehedintu C, et al. The assessment of immunohistochemical profile of endometriosis implants, a practical method to appreciate the aggressiveness and recurrence risk of endometriosis. Rom J Morphol Embryol 2015;56:1301-7. 
  34. Piriyev E, Gertz MM, Schiermeier S, Romer T. Significance of Ki67 expression in endometriosis for infertility. Eur J Obstet Gynecol Reprod Biol 2022;272:73-6. https://doi.org/10.1016/j.ejogrb.2022.03.019