Nonhuman Primate Models for Translational Research in Endometriosis

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Nonhuman primates, particularly baboons and rhesus monkeys, are valuable models for studying endometriosis pathogenesis, evolution, and therapeutic interventions due to spontaneous disease occurrence and induction capabilities.

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This paper reviews nonhuman primate models of translational research in endometriosis, focusing on why spontaneous endometriosis in nonhuman primates (including rhesus monkeys and baboons) is valuable for studying inheritance, pathogenesis, evolution, and treatment response. It describes colony-housed inbred rhesus monkeys as a model for inherited spontaneous endometriosis and highlights baboons as particularly useful, with both spontaneous and induced disease; in baboons, intrapelvic injection of menstrual endometrium produces biological changes in the peritoneal cavity and endometrium, enabling cause-effect studies and biomarker or non-invasive diagnostic/drug development research. A major limitation noted is that endometriosis pathogenesis and spontaneous evolution remain poorly understood, and thus models are being used to address gaps rather than fully resolve them. This paper is centrally about endometriosis — it is a focused review of nonhuman primate models (rhesus monkeys and baboons) and how induced and spontaneous endometriosis are studied for translational insight.

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Abstract

Endometriosis, defined as the ectopic presence of endometrial-like cells, is associated with infertility and pelvic pain in women. Whereas pathogenesis and spontaneous evolution of endometriosis are still poorly understood, recurrences after surgical therapy or after medical treatment are common. Spontaneous endometriosis occurs only in women and in nonhuman primates (NHPs). Inbred rhesus monkeys kept in colonies offer an attractive preclinical model to study the inheritance of spontaneous endometriosis. Baboons with spontaneous or induced endometriosis appear to be the best NHP model to study pathogenesis, pathophysiology, spontaneous evolution and new medical treatment options. In baboons, induction of endometriosis after intrapelvic injection of menstrual endometrium leads to biological changes in peritoneal cavity and in endometrium. This induction process may allows the study of cause-effect relationships which may lead to the discovery of new biomarkers for the development of new non-invasive diagnostic tests and drugs that may prevent or treat endometriosis. Similar content being viewed by others

References

Rokitansky C. Über Uterusdriisen-Neubildung, Z. Gesellschaft Aerzte (Wien); 1860;16:577–581. Shaw RW. Endometriosis. In: RW Shaw, WP Soutter, SL Stanton, eds. Gynaecology. New York, NY: Churchill Livingstone; 1992. Cumiskey J, Whyte P, Kelehan P, Gibbons D. A detailed morphologic and immunohistochemical comparison of pre and postmenopausal endometriosis. J Clin Pathol. 2008;61:455–459. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997;67:817–821. Hadfield R, Mardon H, Barlow DH, Kennedy SH. Delay in diagnosis of endometriosis: a survey of women from the USA and the UK. Hum Reprod. 1996;11:878–880. Te Linde RW, Scott RB. Experimental endometriosis. Am J Obstet Gynecol. 1950;60:1147–1173. Story L, Kennedy S. Animal studies in endometriosis: a review. ILAR J. 2004;45:132–138. Dinulescu DM, Ince TA, Quade BJ, Shafer SA, Crowley D, Jacks T. Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med. 2005;11:63–70. Ingelmo JM, Quereda F, Acién P. Intraperitoneal and subcutaneous treatment of experimental endometriosis with recombinant human interferon-alpha-2b in a murine model. Fertil Steril. 1999;71:907–911. Acién P, Quereda F, Campos A, Gomez-Torres MJ, Velasco I, Gutierrez M. Use of intraperitoneal interferon alpha-2b therapy after conservative surgery for endometriosis and postoperative medical treatment with depot gonadotropin-releasing hormone analog: a randomized clinical trial. Fertil Steril. 2002;78:705–711. D’Hooghe TM. Clinical relevance of the baboon as a model for the study of endometriosis. Fertil Steril. 1997;68:613–625. Stevens VC. Some reproductive studies in the baboon. Hum Reprod Update. 1997;3:533–540. Merrill JA. Spontaneous endometriosis in the Kenya baboon (Papio doguera). Am J Obstet Gynecol. 1968;101:569–570. MacKenzie WF, Casey HW. Animal model of human disease. Endometriosis. Animal model: endometriosis in rhesus monkeys. Am J Pathol. 1975;80:341–344. D’Hooghe TM, Bambra CS, Cornillie FJ, Isahakia M, Koninckx PR. Prevalence and laparoscopic appearance of spontaneous endometriosis in the baboon (Papio anubis-Papio cynocephalus). Biol Reprod. 1991;45:411–416. Zondervan KT, Weeks DE, Colman R, et al. Familial aggregation of endometriosis in a large pedigree of rhesus macaques. Hum Reprod. 2004;19:448–455. Jacobson VC. The intraperitoneal transplantation of endometrial tissue in the rabbit. Arch Pathol Lab Med. 1926;1:169–174. Mann DR, Collins DC, Smith MM, Kessler MJ, Gould KG. Treatment of endometriosis in rhesus monkeys: effectiveness of a gonadotropin-releasing hormone agonist compared to treatment with a progestational steroid. J Clin Endocrin Metab. 1986;63:1277–1283. D’Hooghe TM, Bambra CS, Raeymaekers BM, De Jonge I, Lauweryns JM, Koninckx PR. Intrapelvic injection of menstrual endometrium causes endometriosis in baboons (Papio cynocephalus, Papio anubis). Am J Obstet Gynecol. 1995;173: 125–134. D’Hooghe TM, Bambra CS, De Jonge I, Lauweryns JM, Koninckx PR. The prevalence of spontaneous endometriosis in the baboon increases with the time spent in captivity. Acta Obstet Gynecol Scand. 1996;75:98–101. Dick EJ, Hubbard GB, Martin LJ, Leland MM. Record review of baboons with histologically confirmed endometriosis in a large established colony. J Med Primatol. 2003;32:39–47. Kennedy S, Mardon H, Barlow D. Familial endometriosis. J Assist Reprod Genet. 1995;12:32–34. Hadfield R, Yudkin P, Coe C, et al. Risk factors for endometriosis in the rhesus monkey (Macaca mulatta): a case-control study. Hum Reprod Update. 1997;3:109–115. Simpson J, Elias S, Malinak L, Buttram VS Jr. Heritable aspects of endometriosis. Genetic studies. Am J Obstet Gynecol. 1980;137:327–331. Coxhead D, Thomas E. Familial inheritance of endometriosis in a British population. A case control study. J Obstet Gynnaecol. 1993;13:42–44. Moen MH, Magnus P. The familial risk of endometriosis. Acta Obstet Gynecol Scand. 1993;72:560–564. Zondervan KT, Cardon LR, Kennedy SH. The genetic basis of endometriosis. Curr Opin Obstet Gynecol. 2001;13:309–314. Fakis G, Boukouvala S, Kawamura A, Kennedy S. Description of a novel polymorphic gene encoding for arylamine N-acetyltransferase in the rhesus macaque (Macaca mulatta), a model animal for endometriosis. Pharmacogenet Genomics. 2007;17:181–188. Rier SE. The potential role of exposure to environmental toxicants in the pathophysiology of endometriosis. Ann NY Acad Sci. 2002;955:201–212. Guo SW. The association of endometriosis risk and genetic polymorphisms involving dioxin detoxification enzymes: a systematic review. Eur J Obstet Gynecol Reprod Biol. 2006;124:134–143. Falconer H, D’Hooghe T, Fried G. Endometriosis and genetic polymorphisms. Obstet Gynecol Surv. 2007;62:616–628. Birrell AM, Hennessy A, Gillin A, Horvath J, Tiller D. Reproductive and neotal outcomes in captive bred baboons (Papio hamadryas). J Med Primatol. 1996;25:287–293. Einspanier A, Gore MA. Reproduction: definition of a primate model of female fertility. In: Wolfe-Coote S, ed. The Laboratory Primate, Part II: Use of Primate Model in Research. London: Elsevier books; 2005:105–117. Hunnell NA, Rockcastle NJ, McCormick KN, Sinko LK, Sullivan EL, Cameron JL. Physical activity of adult female rhesus monkeys (Macaca mulatta) across the menstrual cycle. Am J Physiol Endocrinol Metab. 2007;292:E1520-E1525. D’Hooghe TM, Bambra CS, Raeymaekers BM, Koninckx PR. The cumulative incidence rate of endometriosis in baboons (Papio anubis, Papio cynocephalus) with an initially normal pelvis is 70% after 30 months. Obstet Gynecol. 1996;88: 462–466. D’Hooghe TM, Hill JA. In: Bronson RA, Alexander NJ, Anderson DJ, Branch DW, Kutteh WH, eds. Immunobiology of endometriosis. Immunology of Reproduction. Cambridge: Blackwell Science; 1996:322–358. D’Hooghe TM, Nugent N, Cuneo S, et al. Recombinant human TNF binding protein (r-hTBP-1) inhibits the development of endometriosis in baboons: a prospective, randomised, placebo and drug controlled study. Biol Reprod. 2006;74:131–136. Kyama CM, Overbergh L, Mihalyi A, et al. Effect of recombinant human TNF-binding protein-1 and GnRH antagonist on mRNA expression of inflammatory cytokines and adhesion and growth factors in endometrium and endometriosis tissues in baboons. Fertil Steril. 2008;89:1306–1313. D’Hooghe TM, Bambra CS, Xiao L, Hill JA. The effect of menstruation and intrapelvic injection of endometrium on peritoneal fluid parameters in the baboon. Am J Obstet Gynecol. 2001;184:917–925. Overbergh L, Kyama CM, Valckx D, et al. Validation of real time RT-PCR assays for mRNA quantification in baboons. Cytokine. 2005;31:454–458. Fazleabas AT, Brudney A, Chai D, Langoi D, Bulun SE. Steroid receptor and aromatase expression in baboon endometriotic lesions. Fertil Steril. 2003;80:820–827. D’Hooghe TM, Kyama C, Debrock S, Meuleman C, Mwenda JM. The future of endometriosis research. Ann NY Acad Sci. 2004;1034:316–325. Nyachieo A, Chai DC, Deprest J, Mwenda JM, D’Hooghe TM. The baboon as a research model for the study of endometrial biology, uterine receptivity and embryo implantation. Gynecol Obstet Invest. 2007;64:149–155. Chai D, Cuneo S, Falconer H, Mwenda JM, D’Hooghe T. Olive baboon (Papio anubis anubis) as a model for intrauterine research. J Med Primatol. 2007;36:365–369. Cornillie FJ, D’Hooghe TM, Bambra CS, Lauweryns JM, Isahakia M, Koninckx PR. Morphological characteristics of spontaneous endometriosis in the baboon (Papio anubis, Papio Cynocephalus). Gynecol Obstet Invest. 1992;34:225–228. Coe CL, Lemieux AM, Rier SE, Uno H, Zimbric ML. Profile of endometriosis in the aging female rhesus monkey. J Gerontol A Biol Sci Med Sci. 1998;53:M3-M7. Wiegerinck MA, Van Dop PA, Brosens IA. The staging of peritoneal endometriosis by the type of active lesion in addition to the revised American Fertility Society classification. Fertil Steril. 1993;60:461–464. D’Hooghe TM, Bambra CS, Koninckx PR. Cycle fecundity in baboons of proven fertility with minimal endometriosis. Gynecol Obstet Invest. 1994;37:63–65. American Fertility Society: Revised American Fertility Society Classification of Endometriosis. Fertil Steril. 1985;43: 351–352. Falconer H, Mwenda JM, Chai DC, et al. Treatment with anti-TNF monoclonal antibody (c5N) reduces the extent of induced endometriosis in the baboon. Hum Reprod. 2006;21:1856–1862. Lebovic DI, Mwenda JM, Chai DC, et al. PPAR-gamma receptor ligand induces regression of endometrial explants in baboons: a prospective, randomized, placebo- and drug-controlled study. Fertil Steril. 2007;88:1108–1119. D’Hooghe TM. Immunomodulators and aromatase inhibitors: are they the next generation of treatment for endometriosis? Curr Opin Obstet Gynecol. 2003;15:243–249. Mihalyi A, Simsa P, Mutinda KC, Meuleman C, Mwenda JM, D’Hooghe TM. Emerging drugs in endometriosis. Expert Opin Emerg Drugs. 2006;11:503–524. Barrier BF, Bates GW, Leland MM, Leach DA, Robinson RD, Propst AM. Efficacy of anti-tumor necrosis factor therapy in the treatment of spontaneous endometriosis in baboons. Fertil Steril. 2004;81:775–779. D’Hooghe TM, Bambra CS, Raeymaekers BM, Riday AM, Suleman MA, Koninckx PR. The cycle pregnancy rate is normal in baboons with stage I endometriosis but decreased in primates with stage II and stage III-IV disease. Fertil Steril. 1996;66:809–813. Amboka JN, Mwethera PG. Characterization of semen from olive baboons. J Med Primatol. 2003;32:325–329. D’Hooghe TM, Bambra CS, Raeymaekers BM, Koninckx PR. Increased incidence and recurrence of recent corpus luteum without ovulation stigma (luteinized unruptured follicle syndrome?) in baboons with endometriosis. J Soc Gynecol Invest. 1996;3:140–144. Gashaw I, Hastings JM, Jackson KS, Winterhager E, Fazleabas AT. Induced endometriosis in the baboon (Papio anubis) increases the expression of the proangiogenic factor CYR61 (CCN1) in eutopic and ectopic endometria. Biol Reprod. 2006;74:1060–1066. D’Hooghe TM, Bambra CS, Raeymaekers BM, et al. Increased incidence and recurrence of retrograde menstruation in baboons with spontaneous endometriosis. Hum Reprod. 1996;11:2022–2025. D’Hooghe TM, Bambra CS, Raeymaekers BM, Koninckx PR. Serial laparoscopies over 30 months show that endometriosis in captive baboons (Papio anubis, Papio cynocephalus) is a progressive disease. Fertil Steril. 1996;65: 645–649. D’Hooghe TM, Bambra CS, Raeymaekers BM, Hill JA. Pelvic inflammation induced by diagnostic laparoscopy in baboons. Fertil Steril. 1999;72:1134–1141. D’Hooghe TM, Bambra CS, Hill JA, Koninckx PR. Effect on endometriosis and the menstrual cycle on white blood cell subpopulations in the peripheral blood and peritoneal of baboons. Hum Reprod. 1996;11:1736–1740. Falconer H, Bambra CS, Chai D, Cornillie FJ, Hill JA, D’Hooghe TM. The effect of endometriosis, cycle stage, lymphocyte suppression and pregnancy on CA-125 levels in peritoneal fluid and serum in baboons. Hum Reprod. 2005;20:3033–3038. Jackson KS, Brudney A, Hastings JM, Mavrogianis PA, Kim JJ, Fazleabas AT. The altered distribution of the steroid hormone receptors and the chaperone immunophilin FKBP52 in a baboon model of endometriosis is associated with progesterone resistance during the window of uterine receptivity. Reprod Sci. 2007;14:137–150. Hastings M, Jakson S, Mavrogianis P, et al. The estrogen early response gene FOS is altered in baboon model of endometriosis. Biol Reprod. 2006;75:176–182. Kim JJ, Fazleabas T. Uterine receptivity and implantation: the regulation and action of insulin-like growth factor binding protein-1 (HOXA10) and Forkhead transcription factor-1 (FOXO-1) in the baboon endometrium. Reprod Biol Endocrinol. 2004;2:34. Kim JJ, Taylor HS, Lu Z, et al. Altered expression of HOXA10 in endometriosis: potential role in decidualization. Mol Hum Reprod. 2007;13:323–332. D’Hooghe TM, Bambra CS, Raeymaekers BM, De Jonge I, Hill JA, Koninckx PR. The effects of immunosuppression on development and progression of endometriosis in baboons (Papio anubis). Fertil Steril. 1995;64:172–178. Zondervan K, Cardon L, Desrosiers R, et al. The genetic epidemiology of spontaneous endometriosis in the rhesus monkey. Ann NY Acad Sci. 2002;955:233–238. e1. http://www.pjbpubs.com/pharmaprojects/index.htm; Pharmaprojects, V5.1. Accessed April 4, 2006. e2.http://www.medicalnewstoday.com/articles/22446.php. Discontinuation of onercept in moderate-to-severe psoriasis and canvaxin(reg) in stage IV melanoma. Dermatology News. Accessed April 9, 2006. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article D’Hooghe, T.M., Kyama, C.M., Chai, D. et al. Nonhuman Primate Models for Translational Research in Endometriosis. Reprod. Sci. 16, 152–161 (2009). https://doi.org/10.1177/1933719108322430 Published: Issue date: DOI: https://doi.org/10.1177/1933719108322430

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endometriosischronic_pelvic_pain

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Biomedical Research Biomedical Research Biomedical Research Disease Models, Animal Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Macaca mulatta Papio Animals Female Fertility Agents, Female Fertility Agents, Female Humans Immunologic Factors Immunologic Factors Immunosuppressive Agents Immunosuppressive Agents

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