The Effect of Mesenchymal Stem Cells on Fertility in Experimental Retrocervical Endometriosis

 

 Permissions and Reprints

Abstract

Purpose To evaluate the effect of mesenchymal stem cells (MSCs) on fertility in experimental retrocervical endometriosis.

Methods A total of 27 New Zealand rabbits were divided into three groups: endometriosis, in which endometrial implants were created; mesenchymal, in which MSCs were applied in addition to the creation of endometrial implants; and control, the group without endometriosis. Fisher's exact test was performed to compare the dichotomous qualitative variables among the groups. The quantitative variables were compared by the nonparametric Mann-Whitney and Kruskal-Wallis tests. The Mann-Whitney test was used for post-hoc multiple comparison with Boniferroni correction.

Results Regarding the beginning of the fertile period, the three groups had medians of 14 ± 12.7, 40 ± 5, and 33 ± 8.9 days respectively (p = 0.005). With regard to fertility (number of pregnancies), the endometriosis and control groups showed a rate of 77.78%, whereas the mesenchymal group showed a rate of 11.20% (p = 0.015). No differences in Keenan's histological classification were observed among the groups (p = 0.730). With regard to the macroscopic appearance of the lesions, the mesenchymal group showed the most pelvic adhesions.

Conclusion The use of MSCs in endometriosis negatively contributed to fertility, suggesting the role of these cells in the development of this disease.

Resumo

Objetivo Avaliar o efeito das células-tronco mesenquimais sobre a fertilidade na endometriose retrocervical experimental.

Métodos Um total de 27 coelhas da raça Nova Zelândia foram divididas em três grupos: endometriose, em que os implantes endometriais foram criados; mesenquimal, em que as células-tronco mesenquimais foram aplicadas complementarmente à criação implantes endometriais; e controle, sem endometriose. O teste exato de Fisher foi realizado para comparar variáveis dicotômicas qualitativas entre os grupos. As variáveis quantitativas foram comparadas pelos testes não paramétricos de Mann-Whitney e Kruskal-Wallis. O teste de Mann-Whitney foi utilizado para a comparação múltipla pós-hoc com correção de Boniferroni.

Resultados em relação ao início do período fértil, os grupos endometriose, mesenquimal e controle tiveram medianas de 14 ± 12,7; 40 ± 5; e 33 ± 8,9 dias, respectivamente (p = 0,005). Sobre a taxa de fertilidade (número de gravidezes), os grupos endometriose e controle mostraram uma taxa de 77,78%, enquanto o grupo mesenquimal mostrou uma taxa de 11,20% (p = 0,015). Não foram observadas diferenças na classificação histológica de Keenan entre os grupos (p = 0,730). No que diz respeito à aparência macroscópica das lesões, o grupo mesenquimal mostrou maiores adesões pélvicas.

Conclusão O uso de células-tronco mesenquimais na endometriose contribuiu negativamente para a fertilidade, sugerindo o papel dessas células no desenvolvimento da doença.

• References

• 1 Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril 2012; 98 (03) 511-519
  CrossrefPubMedGoogle Scholar
• 2 Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril 1997; 68 (04) 585-596
  CrossrefPubMedGoogle Scholar
• 3 Lafay Pillet MC, Huchon C, Santulli P, Borghese B, Chapron C, Fauconnier A. A clinical score can predict associated deep infiltrating endometriosis before surgery for an endometrioma. Hum Reprod 2014; 29 (08) 1666-1676
  CrossrefPubMedGoogle Scholar
• 4 Porto BTC, Ribeiro HSAA, Galvão MAL, Sekula VG, Aldrigui JM, Ribeiro PAA. [Histological classification and quality of life in women with endometriosis]. Rev Bras Ginecol Obstet 2015; 37 (02) 87-93
  CrossrefPubMedGoogle Scholar
• 5 Stratton P. The association of clinical symptoms with deep infiltrating endometriosis: the importance of the preoperative clinical assessment. Hum Reprod 2014; 29 (08) 1627-1628
  CrossrefPubMedGoogle Scholar
• 6 Oliveira R, Musich DS, Ferreira MPSF, Vilarino FL, Barbosa CP. Perfil epidemiológico das pacientes inférteis com endometrioses. Reprod Clim 2015; 30 (01) 5-10
  PubMedGoogle Scholar
• 7 Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am 1997; 24 (02) 235-258
  CrossrefPubMedGoogle Scholar
• 8 Li T, He H, Liu R, Wang SX, Pu DM. Isolation and identification of epithelial and stromal stem cells from eutopic endometrium of women with endometriosis. Eur J Obstet Gynecol Reprod Biol 2014; 178: 89-94
  CrossrefPubMedGoogle Scholar
• 9 Figueira PGM, Abrão MS, Krikun G, Taylor HS. Stem cells in endometrium and their role in the pathogenesis of endometriosis. Ann N Y Acad Sci 2011; 1221: 10-17
  CrossrefPubMedGoogle Scholar
• 10 Jing Z, Qiong Z, Yonggang W, Yanping L. Rat bone marrow mesenchymal stem cells improve regeneration of thin endometrium in rat. Fertil Steril 2014; 101 (02) 587-594
  CrossrefPubMedGoogle Scholar
• 11 Chan RW, Schwab KE, Gargett CE. Clonogenicity of human endometrial epithelial and stromal cells. Biol Reprod 2004; 70 (06) 1738-1750
  CrossrefPubMedGoogle Scholar
• 12 Gargett CE. Stem cells in gynaecology. Aust N Z J Obstet Gynaecol 2004; 44 (05) 380-386
  CrossrefPubMedGoogle Scholar
• 13 Deane JA, Gualano RC, Gargett CE. Regenerating endometrium from stem/progenitor cells: is it abnormal in endometriosis, Asherman's syndrome and infertility?. Curr Opin Obstet Gynecol 2013; 25 (03) 193-200
  CrossrefPubMedGoogle Scholar
• 14 Du H, Taylor HS. Stem cells and female reproduction. Reprod Sci 2009; 16 (02) 126-139
  CrossrefPubMedGoogle Scholar
• 15 Vidane AS, Zomer HD, Oliveira BMM. , et al. Reproductive stem cell differentiation: extracellular matrix, tissue microenvironment, and growth factors direct the mesenchymal stem cell lineage commitment. Reprod Sci 2013; 20 (10) 1137-1143
  CrossrefPubMedGoogle Scholar
• 16 Dhesi AS, Morelli SS. Endometriosis: a role for stem cells. Womens Health (Lond) 2015; 11 (01) 35-49
  CrossrefPubMedGoogle Scholar
• 17 Mundra V, Gerling IC, Mahato RI. Mesenchymal stem cell-based therapy. Mol Pharm 2013; 10 (01) 77-89
  CrossrefPubMedGoogle Scholar
• 18 Doorn J, Moll G, Le Blanc K, van Blitterswijk C, de Boer J. Therapeutic applications of mesenchymal stromal cells: paracrine effects and potential improvements. Tissue Eng Part B Rev 2012; 18 (02) 101-115
  CrossrefPubMedGoogle Scholar
• 19 do Amaral VF, Dal Lago EA, Kondo W, Souza LC, Francisco JC. Development of an experimental model of endometriosis in rats. Rev Col Bras Cir 2009; 36 (03) 250-255
  CrossrefPubMedGoogle Scholar
• 20 De Miguel MP, Fuentes-Julián S, Blázquez-Martínez A. , et al. Immunosuppressive properties of mesenchymal stem cells: advances and applications. Curr Mol Med 2012; 12 (05) 574-591
  CrossrefPubMedGoogle Scholar
• 21 Howard-Jones N. A CIOMS ethical code for animal experimentation. WHO Chron 1985; 39 (02) 51-56
  PubMedGoogle Scholar
• 22 Schor E, Freitas V, Soares Júnior JM, Simões MJ, Baracat EC. Endometriosis: experimental model in rats. Rev Bras Ginecol Obstet 1999; 21 (05) 281-284
  CrossrefPubMedGoogle Scholar
• 23 Risi E. Control of reproduction in ferrets, rabbits and rodents. Reprod Domest Anim 2014; 49 (Suppl. 02) 81-86
  CrossrefPubMedGoogle Scholar
• 24 Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl 1968; 97: 77-89
  PubMedGoogle Scholar
• 25 Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU. In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res 1998; 238 (01) 265-272
  CrossrefPubMedGoogle Scholar
• 26 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 (01) 135-141
  CrossrefPubMedGoogle Scholar
• 27 Amaral VF, Maestrelli PC, Francisco JC. , et al. Bone marrow derived mononuclear stromal cells and experimental model of deep endometriosis. Int J Clin Exp Pathol 2016; 9 (02) 1116-1126
  PubMedGoogle Scholar
• 28 Matsuzaki S, Darcha C. Epithelial to mesenchymal transition-like and mesenchymal to epithelial transition-like processes might be involved in the pathogenesis of pelvic endometriosis. Hum Reprod 2012; 27 (03) 712-721
  CrossrefPubMedGoogle Scholar
• 29 Du X, Yuan Q, Qu Y, Zhou Y, Bei J. Endometrial mesenchymal stem cells isolated from menstrual blood by adherence. Stem Cells Int 2016; 2016: 3573846
  PubMedGoogle Scholar
• 30 Revised American Society for Reproductive Medicine Classification of Endometriosis. Fertil Steril 1996; 67 (05) 817-821
  PubMed
• 31 de Ziegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and management. Lancet 2010; 376 (9742): 730-738
  CrossrefPubMedGoogle Scholar