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Laparoscopic Surgery: A New Technique to Induce Endometriosis in a Mouse Model

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Abstract

Background

This prospective pilot study was designed to induce endometriosis in a mouse model using laparoscopy, a less invasive and more precise approach than laparotomy. We aimed to achieve a peritoneal implant rate of at least 50% by varying both duration of anesthesia and intra-abdominal insufflation pressure.

Methods

Female BALB/cANnCrl mice in metestrus or diestrus were used as donors (n = 5) or recipients (n = 20) of uterine transplant tissue. Each recipient mouse was laparoscopically inoculated with 10 uterine pieces (range: 10-12) from donor mice into the abdominal cavity. Before starting the study, recipient mice were randomly assigned to 4 groups with variable duration of anesthesia (ketamine/xylazine or pentobarbital) and variable intra-abdominal pressure (5 or 15 mm Hg). One week after laparoscopy, endometriosis incidence and peritoneal implant take rate were documented visually during laparotomy. The retrieved lesions were histologically analyzed.

Results

Laparoscopic inoculation of uterine pieces in recipient mice resulted in an endometriosis incidence of 100% (20/20 animals) and an individual peritoneal implant take rate of 60% (121/206), ranging from 17% (2/12) till 83% (10/12), without differences between the 4 subgroups, and with a histological confirmation rate of 92% (58/63).

Conclusions

To the best our knowledge, this is the first report showing that endometriosis can be induced by laparoscopic surgery in rodents, with a 100% incidence and a median peritoneal implant take rate of 60%. This laparoscopic model offers important advantages over traditional laparotomy models that are limited by surgery-associated trauma and/or adhesion formation.

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References

  1. Giudice, LC, Kao, LC Endometriosis. Lancet. 2004;364(9447): 1789–1799.

    Google Scholar 

  2. Sampson, JA Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol. 1927;14(4):422–469.

    Article  Google Scholar 

  3. Olovsson, M Immunological aspects of endometriosis: an update. Am J Reprod Immunol. 2011;66(suppl 1):101–104.

    Article  PubMed  Google Scholar 

  4. Khoufache, K, Michaud, N, Harir, N, Kibangou Bondza, P, Akoum, A Anomalies in the inflammatory response in endometriosis and possible consequences: a review. Minerva Endocrinol. 2012; 37(1):75–92.

    CAS  PubMed  Google Scholar 

  5. Hadfield, R, Mardon, H, Barlow, D, Kennedy, S Delay in the diag-nosis of endometriosis: a survey of women from the USA and the UK Hum Reprod. 1996;11(4):878–880.

    CAS  Google Scholar 

  6. Pullen, N, Birch, CL, Douglas, GJ, Hussain, Q, Pruimboom-Brees, I, Walley, RJ The translational challenge in the development of new and effective therapies for endometriosis: a review of confidence from published preclinical efficacy studies. Hum Reprod Update. 2011;17(6):791–802.

    Article  PubMed  Google Scholar 

  7. Grummer, R Animal models in endometriosis research. Hum Reprod Update. 2006;12(5):641–649.

    Article  PubMed  Google Scholar 

  8. Greaves, E, Cousins, FL, Murray, A, et al. A novel mouse model of endometriosis mimics human phenotype and reveals insights into the inflammatory contribution of shed endometrium. Am J Pathol. 2014;184(7):1930–1939.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Grummer, R, Schwarzer, F, Bainczyk, K, et al. Peritoneal endome-triosis: validation of an in-vivo model. Hum Reprod. 2001;16(8): 1736–1743.

    Article  CAS  PubMed  Google Scholar 

  10. Herington, JL, Crispens, MA, Carvalho-Macedo, AC, et al. Devel-opment and prevention of postsurgical adhesions in a chimeric mouse model of experimental endometriosis. Fertil Steril. 2011; 95(4):1295–1301.e1.

    Article  PubMed  Google Scholar 

  11. Hsiao, KY, Chang, N, Lin, SC, Li, YH, Wu, MH Inhibition of dual specificity phosphatase-2 by hypoxia promotes interleukin-8-mediated angiogenesis in endometriosis. Hum Reprod. 2014; 29(12):2747–2755.

    Article  CAS  PubMed  Google Scholar 

  12. Nothnick, WB, Graham, A, Holbert, J, Weiss, MJ miR-451 defi-ciency is associated with altered endometrial fibrinogen alpha chain expression and reduced endometriotic implant establishment in an experimental mouse model. PLoS One. 2014;9(6): e100336.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Binda, MM, Molinas, CR, Hansen, P, Koninckx, PR Effect of desiccation and temperature during laparoscopy on adhesion formation in mice. Fertil Steril. 2006;86(1):166–175.

    Article  PubMed  Google Scholar 

  14. D’Hooghe, TM, Bambra, CS, Raeymaekers, BM, De Jonge, I, Lau-weryns, JM, Koninckx, PR Intrapelvic injection of menstrual endo-metrium causes endometriosis in baboons (Papio cynocephalus and Papio anubis). Am J Obstet Gynecol. 1995;173(1):125–134.

    Article  PubMed  Google Scholar 

  15. Lovell, DP Variation in pentobarbitone sleeping time in mice. 1. Strain and sex differences. Lab Anim. 1986;20(2):85–90.

    Article  CAS  PubMed  Google Scholar 

  16. Buitrago, S, Martin, TE, Tetens-Woodring, J, Belicha-Villanueva, A, Wilding, GE Safety and efficacy of various combinations of injectable anesthetics in BALB/c mice. J Am Assoc Lab Anim Sci. 2008;47(1):11–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Nisolle, M, Casanas-Roux, F, Donnez, J Early-stage endometriosis: adhesion and growth of human menstrual endometrium in nude mice. Fertil Steril. 2000;74(2):306–312.

    Article  CAS  PubMed  Google Scholar 

  18. Bruner-Tran, KL, Osteen, KG, Duleba, AJ Simvastatin protects against the development of endometriosis in a nude mouse model. J Clin Endocrinol Metab. 2009;94(7):2489–2494.

    Article  CAS  PubMed  Google Scholar 

  19. Yelian, FD, Shavell, VI, Diamond, MP Early demonstration of postoperative adhesions in a rodent model. Fertil Steril. 2010; 93(8):2734–2737.

    Article  PubMed  Google Scholar 

  20. Bove, GM, Chapelle, SL Visceral mobilization can lyse and pre-vent peritoneal adhesions in a rat model. J Bodyw Mov Ther. 2012;16(1):76–82.

    Article  PubMed  Google Scholar 

  21. Volz, J, Koster, S, Spacek, Z, Paweletz, N Characteristic alterations of the peritoneum after carbon dioxide pneumoperitoneum. Surg Endosc. 1999;13(6):611–614.

    Article  CAS  PubMed  Google Scholar 

  22. Molinas, CR, Mynbaev, O, Pauwels, A, Novak, P, Koninckx, PR Peritoneal mesothelial hypoxia during pneumoperitoneum is a cofactor in adhesion formation in a laparoscopic mouse model. Fertil Steril. 2001;76(3):560–567.

    Article  CAS  PubMed  Google Scholar 

  23. Emanuele, MA, Wezeman, F, Emanuele, NV Alcohol’s effects on female reproductive function. Alcohol Res Health. 2002;26(4): 274–281.

    PubMed  PubMed Central  Google Scholar 

  24. Fish, RE, Brown, MJ, Danneman, PJ, Karas, AZ Anesthesia and Analgesia in Laboratory Animals. Philadelphia, PA: Elsevier Inc; 2008.

    Google Scholar 

  25. Pera, M, Nelson, H, Rajkumar, SV, Young-Fadok, TM, Burgart, LJ Influence of postoperative acute-phase response on angiogenesis and tumor growth: open vs. laparoscopic-assisted surgery in mice. J Gastrointest Surg. 2003;7(6):783–790.

    Article  PubMed  Google Scholar 

  26. Karayiannakis, AJ, Makri, GG, Mantzioka, A, Karousos, D, Karatzas, G Systemic stress response after laparoscopic or open cholecystectomy: a randomized trial. Br J Surg. 1997; 84(4):467–471.

    CAS  PubMed  Google Scholar 

  27. Suematsu, T, Hirabayashi, Y, Shiraishi, N, Adachi, Y, Kitamura, H, Kitano, S Morphology of the murine peritoneum after pneumo-peritoneum vs laparotomy. Surg Endosc. 2001;15(9):954–958.

    Article  CAS  PubMed  Google Scholar 

  28. Balague, C, Targarona, EM, Pujol, M, Filella, X, Espert, JJ, Trias, M Peritoneal response to a septic challenge. Comparison between open laparotomy, pneumoperitoneum laparoscopy, and wall lift laparoscopy. Surg Endosc. 1999;13(8):792–796.

    Article  CAS  PubMed  Google Scholar 

  29. Schippers, E, Tittel, A, Ottinger, A, Schumpelick, V Laparo-scopy versus laparotomy: comparison of adhesion-formation after bowel resection in a canine model. Dig Surg. 1998; 15(2):145–147.

    Article  CAS  PubMed  Google Scholar 

  30. Burney, RO, Giudice, LC Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98(3):511–519.

    Article  CAS  PubMed  Google Scholar 

  31. van der Linden, PJ, de Goeij, AF, Dunselman, GA, Erkens, HW, Evers, JL Endometrial cell adhesion in an in vitro model using intact amniotic membranes. Fertil Steril. 1996;65(1):76–80.

    Article  PubMed  Google Scholar 

  32. Korbel, C, Menger, MD, Laschke, MW Size and spatial orientation of uterine tissue transplants on the peritoneum crucially determine the growth and cyst formation of endometriosis-like lesions in mice. Hum Reprod. 2010;25(10):2551–2558.

    Article  PubMed  Google Scholar 

  33. Gakhar, G, Wight-Carter, M, Andrews, G, Olson, S, Nguyen, TA Hydronephrosis and urine retention in estrogen-implanted athy-mic nude mice. Vet Pathol. 2009;46(3):505–508.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Leuven University Fertility Centre, University Hospital Leuven, Leuven, Belgium

    Daniëlle P. Peterse MSc, Amelie Fassbender PhD & F. O. Dorien MSc

  2. Department of Development and Regeneration, Laboratory of Experimental Gynaecology, Leuven University, Herestraat 49, Leuven, 3000, Belgium

    Daniëlle P. Peterse MSc, Amelie Fassbender PhD, Arne Vanhie MD, Joris Vriens PhD, M. Mercedes Binda PhD & Thomas M. D’Hooghe MD, PhD

  3. MRC Centre for Inflammation Research, The University of Edinburgh, Edinburgh, Scotland, UK

    Philippa Saunders PhD

  4. Division of Reproductive Biology, Institute of Primate Research, Nairobi, Kenya

    Thomas M. D’Hooghe MD, PhD

Authors
  1. Daniëlle P. Peterse MSc
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  2. Amelie Fassbender PhD
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  3. F. O. Dorien MSc
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  4. Arne Vanhie MD
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  7. M. Mercedes Binda PhD
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  8. Thomas M. D’Hooghe MD, PhD
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Corresponding author

Correspondence to Thomas M. D’Hooghe MD, PhD.

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Peterse, D.P., Fassbender, A., Dorien, F.O. et al. Laparoscopic Surgery: A New Technique to Induce Endometriosis in a Mouse Model. Reprod. Sci. 23, 1332–1339 (2016). https://doi.org/10.1177/1933719116638178

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  • DOI: https://doi.org/10.1177/1933719116638178

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