Skip to main content

Advertisement

Log in

Effect of induced peritoneal endometriosis on oocyte and embryo quality in a mouse model

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To assess the impact of peritoneal endometriosis on oocyte and embryo quality in a mouse model.

Methods

Peritoneal endometriosis was surgically induced in 33 B6CBA/F1 female mice (endometriosis group, N = 17) and sham-operated were used as control (sham group, N = 16). Mice were superovulated 4 weeks after surgery and mated or not, to collect E0.5-embryos or MII-oocytes. Evaluation of oocyte and zygote quality was done by immunofluorescence under spinning disk confocal microscopy.

Results

Endometriosis-like lesions were observed in all mice of endometriosis group. In both groups, a similar mean number of MII oocytes per mouse was observed in non-mated mice (30.2 vs 32.6), with a lower proportion of normal oocytes in the endometriosis group (61 vs 83 %, p < 0.0001). Abnormalities were incomplete extrusion or division of the first polar body and spindle abnormalities. The mean number of zygotes per mouse was lower in the endometriosis group (21 vs 35.5, p = 0.02) without difference in embryo quality.

Conclusions

Our results support that induced peritoneal endometriosis in a mouse model is associated with a decrease in oocyte quality and embryo number. This experimental model allows further studies to understand mechanisms of endometriosis-associated infertility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Practice Committee of the American Society for Reproductive Medicine. Endometriosis and infertility. Fertil Steril. 2004;82 Suppl 1:S40–5.

    Google Scholar 

  2. Witz CA, Burns WN. Endometriosis and infertility: is there a cause and effect relationship? Gynecol Obstet Investig. 2002;53 Suppl 1:2–11.

    Article  Google Scholar 

  3. Porpora MG, Pultrone DC, Bellavia M, Franco C, Crobu M, Cosmi EV. Reproductive outcome after laparoscopic treatment of endometriosis. Clin Exp Obstet Gynecol. 2002;29:271–3.

    CAS  PubMed  Google Scholar 

  4. Jacobson TZ, Duffy JM, Barlow D, Farquhar C, Koninckx PR, Olive D. Laparoscopic surgery for subfertility associated with endometriosis. Cochrane Database Syst Rev. 2010: CD001398.

  5. Marcoux S, Maheux R, Berube S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian collaborative group on endometriosis. N Engl J Med. 1997;337:217–22.

    Article  CAS  PubMed  Google Scholar 

  6. Parazzini F. Ablation of lesions or no treatment in minimal-mild endometriosis in infertile women: a randomized trial. Gruppo Italiano per lo studio dell’Endometriosi. Hum Reprod. 1999;14:1332–4.

    Article  CAS  PubMed  Google Scholar 

  7. Halme J, Becker S, Hammond MG, Raj MH, Raj S. Increased activation of pelvic macrophages in infertile women with mild endometriosis. Am J Obstet Gynecol. 1983;145:333–7.

    CAS  PubMed  Google Scholar 

  8. Rana N, Braun DP, House R, Gebel H, Rotman C, Dmowski WP. Basal and stimulated secretion of cytokines by peritoneal macrophages in women with endometriosis. Fertil Steril. 1996;65:925–30.

    CAS  PubMed  Google Scholar 

  9. Wang Y, Sharma RK, Falcone T, Goldberg J, Agarwal A. Importance of reactive oxygen species in the peritoneal fluid of women with endometriosis or idiopathic infertility. Fertil Steril. 1997;68:826–30.

    Article  CAS  PubMed  Google Scholar 

  10. Oosterlynck DJ, Meuleman C, Waer M, Vandeputte M, Koninckx PR. The natural killer activity of peritoneal fluid lymphocytes is decreased in women with endometriosis. Fertil Steril. 1992;58:290–5.

    CAS  PubMed  Google Scholar 

  11. Yoshida S, Harada T, Iwabe T, Taniguchi F, Mitsunari M, Yamauchi N, et al. A combination of interleukin-6 and its soluble receptor impairs sperm motility: implications in infertility associated with endometriosis. Hum Reprod. 2004;19:1821–5.

    Article  CAS  PubMed  Google Scholar 

  12. Mansour G, Aziz N, Sharma R, Falcone T, Goldberg J, Agarwal A. The impact of peritoneal fluid from healthy women and from women with endometriosis on sperm DNA and its relationship to the sperm deformity index. Fertil Steril. 2009;92:61–7.

    Article  CAS  PubMed  Google Scholar 

  13. Perdichizzi A, Nicoletti F, La Vignera S, Barone N, D’Agata R, Vicari E, et al. Effects of tumour necrosis factor-alpha on human sperm motility and apoptosis. J Clin Immunol. 2007;27:152–62.

    Article  CAS  PubMed  Google Scholar 

  14. Mansour G, Sharma RK, Agarwal A, Falcone T. Endometriosis-induced alterations in mouse metaphase II oocyte microtubules and chromosomal alignment: a possible cause of infertility. Fertil Steril. 2010;94:1894–9.

    Article  PubMed  Google Scholar 

  15. Banerjee J, Sharma R, Agarwal A, Maitra D, Diamond MP, Abu-Soud HM. IL-6 and mouse oocyte spindle. PLoS One. 2012;7:e35535.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Piromlertamorn W, Saeng-anan U, Vutyavanich T. Effects of ovarian endometriotic fluid exposure on fertilization rate of mouse oocytes and subsequent embryo development. Reprod Biol Endocrinol. 2013;11:4.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Moon CE, Bertero MC, Curry TE, London SN, Muse KN, Sharpe KL, et al. The presence of luteinized unruptured follicle syndrome and altered folliculogenesis in rats with surgically induced endometriosis. Am J Obstet Gynecol. 1993;169:676–82.

    Article  CAS  PubMed  Google Scholar 

  18. Stilley JA, Woods-Marshall R, Sutovsky M, Sutovsky P, Sharpe-Timms KL. Reduced fecundity in female rats with surgically induced endometriosis and in their daughters: a potential role for tissue inhibitors of metalloproteinase 1. Biol Reprod. 2009;80:649–56.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Pal AK, Biswas S, Goswami SK, Kabir SN. Effect of pelvic endometrial implants on overall reproductive functions of female rats. Biol Reprod. 1999;60:954–8.

    Article  CAS  PubMed  Google Scholar 

  20. Vernon MW, Wilson EA. Studies on the surgical induction of endometriosis in the rat. Fertil Steril. 1985;44:684–94.

    CAS  PubMed  Google Scholar 

  21. Barragan JC, Brotons J, Ruiz JA, Acien P. Experimentally induced endometriosis in rats: effect on fertility and the effects of pregnancy and lactation on the ectopic endometrial tissue. Fertil Steril. 1992;58:1215–9.

    CAS  PubMed  Google Scholar 

  22. Furukubo M, Fujino Y, Umesaki N, Ogita S. Effects of endometrial stromal cells and peritoneal fluid on fertility associated with endometriosis. Osaka City Med J. 1998;44:43–54.

    CAS  PubMed  Google Scholar 

  23. Umezawa M, Saito Y, Tanaka-Hattori N, Takeda K, Ihara T, Sugamata M. Expression profile of extracellular matrix and adhesion molecules in the development of endometriosis in a mouse model. Reprod Sci. 2012;19:1365–72.

    Article  CAS  PubMed  Google Scholar 

  24. Han SJ, Hawkins SM, Begum K, Jung SY, Kovanci E, Qin J, et al. A new isoform of steroid receptor coactivator-1 is crucial for pathogenic progression of endometriosis. Nat Med. 2012;18:1102–11.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Laschke MW, Giebels C, Nickels RM, Scheuer C, Menger MD. Endothelial progenitor cells contribute to the vascularization of endometriotic lesions. Am J Pathol. 2011;178:442–50.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Becker CM, Beaudry P, Funakoshi T, Benny O, Zaslavsky A, Zurakowski D, et al. Circulating endothelial progenitor cells are up-regulated in a mouse model of endometriosis. Am J Pathol. 2011;178:1782–91.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Fang Z, Yang S, Gurates B, Tamura M, Simpson E, Evans D, et al. Genetic or enzymatic disruption of aromatase inhibits the growth of ectopic uterine tissue. J Clin Endocrinol Metab. 2002;87:3460–6.

    Article  CAS  PubMed  Google Scholar 

  28. Rudzitis-Auth J, Menger MD, Laschke MW. Resveratrol is a potent inhibitor of vascularization and cell proliferation in experimental endometriosis. Hum Reprod. 2013;28:1339–47.

    Article  CAS  PubMed  Google Scholar 

  29. Pelch KE, Sharpe-Timms KL, Nagel SC. Mouse model of surgically-induced endometriosis by auto-transplantation of uterine tissue. J Vis Exp. 2012: e3396.

  30. Eroglu A, Toth TL, Toner M. Alterations of the cytoskeleton and polyploidy induced by cryopreservation of metaphase II mouse oocytes. Fertil Steril. 1998;69:944–57.

    Article  CAS  PubMed  Google Scholar 

  31. Schatten G, Simerly C, Schatten H. Microtubule configurations during fertilization, mitosis, and early development in the mouse and the requirement for egg microtubule-mediated motility during mammalian fertilization. Proc Natl Acad Sci U S A. 1985;82:4152–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Boiso I, Marti M, Santalo J, Ponsa M, Barri PN, Veiga A. A confocal microscopy analysis of the spindle and chromosome configurations of human oocytes cryopreserved at the germinal vesicle and metaphase II stage. Hum Reprod. 2002;17:1885–91.

    Article  PubMed  Google Scholar 

  33. Choi WJ, Banerjee J, Falcone T, Bena J, Agarwal A, Sharma RK. Oxidative stress and tumor necrosis factor-alpha-induced alterations in metaphase II mouse oocyte spindle structure. Fertil Steril. 2007;88:1220–31.

    Article  CAS  PubMed  Google Scholar 

  34. Tarin JJ, Vendrell FJ, Ten J, Blanes R, van Blerkom J, Cano A. The oxidizing agent tertiary butyl hydroperoxide induces disturbances in spindle organization, c-meiosis, and aneuploidy in mouse oocytes. Mol Hum Reprod. 1996;2:895–901.

    Article  CAS  PubMed  Google Scholar 

  35. Richter HE, Holley RL, Andrews WW, Owen J, Miller KB. The association of interleukin 6 with clinical and laboratory parameters of acute pelvic inflammatory disease. Am J Obstet Gynecol. 1999;181:940–4.

    Article  CAS  PubMed  Google Scholar 

  36. Bedaiwy MA, Falcone T, Sharma RK, Goldberg JM, Attaran M, Nelson DR, et al. Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Hum Reprod. 2002;17:426–31.

    Article  CAS  PubMed  Google Scholar 

  37. Ebner T, Moser M, Yaman C, Feichtinger O, Hartl J, Tews G. Elective transfer of embryos selected on the basis of first polar body morphology is associated with increased rates of implantation and pregnancy. Fertil Steril. 1999;72:599–603.

    Article  CAS  PubMed  Google Scholar 

  38. De Santis L, Cino I, Rabellotti E, Calzi F, Persico P, Borini A, et al. Polar body morphology and spindle imaging as predictors of oocyte quality. Reprod BioMed Online. 2005;11:36–42.

    Article  PubMed  Google Scholar 

  39. Rienzi L, Ubaldi FM, Iacobelli M, Minasi MG, Romano S, Ferrero S, et al. Significance of metaphase II human oocyte morphology on ICSI outcome. Fertil Steril. 2008;90:1692–700.

    Article  PubMed  Google Scholar 

  40. Choi T, Fukasawa K, Zhou R, Tessarollo L, Borror K, Resau J, et al. The Mos/mitogen-activated protein kinase (MAPK) pathway regulates the size and degradation of the first polar body in maturing mouse oocytes. Proc Natl Acad Sci U S A. 1996;93:7032–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Zhang H, Zhang Y, Zhao H, Zhang Y, Chen Q, Peng H, et al. Hormonal regulation of ovarian bursa fluid in mice and involvement of aquaporins. PLoS One. 2013;8:e63823.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Rodriguez A, Catalan V, Gomez-Ambrosi J, Garcia-Navarro S, Rotellar F, Valenti V, et al. Insulin- and leptin-mediated control of aquaglyceroporins in human adipocytes and hepatocytes is mediated via the PI3K/Akt/mTOR signaling cascade. J Clin Endocrinol Metab. 2011;96:E586–97.

    Article  CAS  PubMed  Google Scholar 

  43. Shahine LK, Burney RO, Behr B, Milki AA, Westphal LM, Lathi RB. Embryo quality before and after surgical treatment of endometriosis in infertile patients. J Assist Reprod Genet. 2009;26:69–73.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Brizek CL, Schlaff S, Pellegrini VA, Frank JB, Worrilow KC. Increased incidence of aberrant morphological phenotypes in human embryogenesis–an association with endometriosis. J Assist Reprod Genet. 1995;12:106–12.

    Article  CAS  PubMed  Google Scholar 

  45. Pellicer A, Oliveira N, Ruiz A, Remohi J, Simon C. Exploring the mechanism(s) of endometriosis-related infertility: an analysis of embryo development and implantation in assisted reproduction. Hum Reprod. 1995;10 Suppl 2:91–7.

    Article  PubMed  Google Scholar 

  46. Grummer R. Animal models in endometriosis research. Hum Reprod Update. 2006;12:641–9.

    Article  PubMed  Google Scholar 

  47. Colette S, Donnez J. Animal models in endometriosis experimental research. Gynecol Obstet Fertil. 2012;40:494–6.

    Article  CAS  PubMed  Google Scholar 

  48. Ertzeid G, Storeng R. The impact of ovarian stimulation on implantation and fetal development in mice. Hum Reprod. 2001;16:221–5.

    Article  CAS  PubMed  Google Scholar 

  49. Rajkumar K, Schott PW, Simpson CW. The rat as an animal model for endometriosis to examine recurrence of ectopic endometrial tissue after regression. Fertil Steril. 1990;53:921–5.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Romain Morichon for the use of the spinning disk confocal microscopy, Michele Oster for the histology, Lauriane Roche for her help in building the figures.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. Cohen.

Additional information

Capsule In a mouse model, peritoneal endometriosis was responsible for decrease in oocyte quality and embryo quantity. Number of ovulated oocytes was not impaired.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cohen, J., Ziyyat, A., Naoura, I. et al. Effect of induced peritoneal endometriosis on oocyte and embryo quality in a mouse model. J Assist Reprod Genet 32, 263–270 (2015). https://doi.org/10.1007/s10815-014-0390-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-014-0390-1

Keywords

Navigation