Experimental Endometriosis in the Rat Is Correlated With Colonic Motor Function Alterations but Not With Bacterial Load

Endometriosis commonly presents with symptoms that mimic chronic gastrointestinal disorders. The authors used the autotransplantion model of endometriosis in rats to investigate the possible underlying mechanisms. After the rats were killed, the presence of endometriotic vesicles, colonic inflammation, and white blood cell (WBC) numbers in the peritoneal fluid was determined. Sections of colon and of jejunum were collected for measurement of myeloperoxidase (MPO) activity and bacterial counts, and isometric recording in response to acetylcholine was measured in segments of longitudinal and circular smooth muscle. Experimental animals had significantly more colonic damage, MPO activity, and WBC numbers than controls did. There was no significant difference in the total bacterial load; however, experimental animals demonstrated an increased tension in the longitudinal muscle, which correlated with WBC numbers and colonic damage. In summary, this study presents evidence for a significant effect of peritoneal endometriosis on colonic function and integrity, which may help explain the gastrointestinal symptoms associated with this disease. Similar content being viewed by others

Zwas FR, Lyon DT Endometriosis: an important condition in clinical gastroenterology. Dig Dis Sci. 1991;36:353–364. Prystowsky JB, Stryker SJ, Ujiki GT, Poticha SM Gastrointestinal endometriosis. Incidence and indications for resection. Arch Surg. 1988;123:855–858. Shah M., Tager D., Feller E. Intestinal endometriosis masquerading as a common digestive disorder. Arch Intern Med. 1995;155:977–980. Skoog SM, Foxx-Orenstein AE, Levy MJ, Session DR Intestinal endometriosis: the great masquerader. Curr Gastroenterol Rep. 2004;6:405–409. Boulton R., Chawla MH, Poole S., Hodgson HG, Barrison IG Ileal endometriosis masquerading as Crohn’s ileitis. J Clin Gastroenterol. 1997;25:338–342. Langlois NE, Park KG, Keenan RA Mucosal changes in the large bowel with endometriosis: a possible cause of misdiagnosis of colitis? Hum Pathol. 1994;25:1030–1034. Lea R., Bancroft K., Whorwell PJ Irritable bowel syndrome, chronic pelvic inflammatory disease and endometriosis: a comparison of symptomatology. Eur J Gastroenterol Hepatol. 2004;16:1269–1272. Blumberg RS, Strober W. Prospects for research in inflammatory bowel disease. JAMA. 2001;285:643–647. Sinha AA, Lopez T., McDevitt HO Autoimmune diseases: the failure of self disease tolerance. Science. 1990;248:1380–1388. Sartor RB Current concepts of the etiology and pathogenesis of ulcerative colitis and crohn’s disease. Inflamm Bowel Dis. 1995;24:475–501. Drossman DA, Camilleri M., Mayer EA, WhiteheadWE.AGA technical review on irritable bowel syndrome. Gastroenterology. 2002;123:2108–2131. Mayer EA, Naliboff BD, Chang L. Basic pathophysiologic mechanism in irritable bowel syndrome. Dig Dis. 2001;19: 212–218. Yantiss RK, Clement PB, Young RH Endometriosis of the intestinal tract: a study of 44 cases of a disease that may cause diverse challenges in clinical and pathologic evaluation. Am J Surg Pathol. 2001;25:445–554. Mathias JR, Franklin R., Quast DC, et al. Relation of endometriosis and neuromuscular disease of the gastrointestinal tract: new insights. Fertil Steril. 1998;70:81–88. Anaf V., Simon P., El Nakadi I., et al. Relationship between endometriotic foci and nerves in rectovaginal endometriotic nodules. Hum Reprod. 2000;15:1744–1750. Coronado C., Franklin RR, Lotze EC, Bailey HR, Valdes CT Surgical treatment of symptomatic colorectal endometriosis. Fertil Steril. 1990;53:411–416. Vernon MW, Beard JS, Graves K., Wilson EA Classification of endometriotic implants by morphologic appearance and capacity to synthesize prostaglandin F. Fertil Steril. 1986;46: 801–806. Anaf V., Chapron C., El Nakadi I., De Moor V., Simonart T., Noel JC Pain, mast cells, and nerves in peritoneal, ovarian, and deep infiltrating endometriosis. Fertil Steril. 2006;86:1336–1343. Rojas-Cartagena C., Appleyard CB, Santiago OI, Flores I. Experimental intestinal endometriosis is characterized by increased levels of soluble TNFRSF1B and downregulation of Tnfrsf1a and Tnfrsf1b gene expression. Biol Reprod. 2005;73: 1211–1218. Hernández GA, Appleyard CB Bacterial load in animal models of acute and chronic “reactivated” colitis. Digestion. 2003; 67:161–169. Bailey MT, Coe CL Endometriosis is associated with an altered profile of intestinal microflora in female rhesus monkeys. Hum Reprod. 2002;17:1704–1708. Schultsz C., Van Den Berg F., Ten Kate F., Tytgat G., Dankert J. The intestinal mucus layer from patients with inflammatory bowel disease harbors high numbers of bacteria compared with controls. Gastroenterology. 1999;117:1089–1097. Hosseini JM, Goldhill JM, Bossone C., Pineiro-Carrero V., Shea-Donohue T. Progressive alterations in circular smooth muscle contractility in TNBS-induced colitis in rats. Neurogastroenterol Motil. 1999;11:347–356. Porras M., Martin MT, Soler M., Vergara P. Intestinal motor disorders associated with cyclical bacterial overgrowth in a rat model of enteritis. Am J Physiol. 2004;287:58–64. Vernon MW, Wilson EA Studies on the surgical induction of endometriosis in the rat. Fertil Steril. 1985;44:684–694. Ingelmo MR, Quereda F., Acién P. Intraperitoneal and subcutaneus treatment of experimental endometriosis with recombinant human interferon-α-2b in a murine model. Fertil Steril. 1999;71:907–911. Appleyard CB, Wallace JL Reactivation of hapten-induced colitis and its prevention by anti-inflammatory drugs. Am J Physiol. 1995;269:G119–G125. Bradley P., Priebat D., Christensen R., Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker.J Invest Dermatol. 1982; 78:206–209. Appleyard CB, Morales M., Percy WH Regional variations in neurokinin receptor subtype contributions to muscularis mucosae and epithelial function in rat colon. Dig Dis Sci. 2006;51:506–516. Myers BS, Martin JS, Dempsey DT, Parkman HP, Thomas RM, Ryan JP Acute experimental colitis decreases colonic circular smooth muscle contractility in rats. Am J Physiol. 1997;273:G928–G936. Bossone C., Hosseini JM, Pinero-Carrero V., Shea-Donohue T. Alterations in spontaneous contractions in vitro after repeated inflammation of rat distal colon. Am J Physiol. 2001;280: G949–G957. Matuk R., Crawford J., Abreu MT, Targan SR, Vasiliauskas EA, Papadakis KA The spectrum of gastrointestinal toxicity and effect on disease activity of selective cyclooxygenase-2 inhibitors in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2004;10:352–356. Sharma SC, Barry-Kinsella C., Cottell E., Harrison R.F. A midluteal phase comparison of peritoneal fluid volume and its content of PGF2 alpha and PGE2 in women with minimal stage endometriosis and a normal pelvis. Prostaglandins 1994;47:9–16. Wu MH, Shoji Y., Wu MC, et al. Suppression of matrix metalloproteinase-9 by prostaglandin E(2) in peritoneal macrophage is associated with severity of endometriosis. Am J Pathol. 2005;167:1061–1069. Grasa L., Arruebo MP, Plaza MA, Murillo MD PGE(2) receptors and their intracellular mechanisms in rabbit small intestine. Prostaglandins Other Lipid Mediat. 2006;79:206–217. Van Hoogmoed LM, Snyder JR, Harmon F. In vitro investigation of the effect of prostaglandins and nonsteroidal anti-inflammatory drugs on contractile activity of the equine smooth muscle of the dorsal colon, ventral colon, and pelvic flexure. Am J Vet Res. 2000;61:1259–1266. Burakoff R., Percy WH Studies in vivo and in vitro on effects of PGE2 on colonic motility in rabbits. Am J Physiol. 1992;262(1 pt 1):G23–G29. Bauer AJ, Boeckxstaens GE Mechanisms of postoperative ileus. Neurogastroenterol Motil. 2004;16(suppl 2):54–60. Fukuda H., Tsuchida D., Koda K., Miyazaki M., Pappas TN, Takahashi T. Impaired gastric motor activity after abdominal surgery in rats. Neurogastroenterol Motil. 2005;17:245–250. Winnard KP, Dmitrieva N., Berkley KJ Cross-organ interactions between reproductive, gastrointestinal, and urinary tracts: modulation by estrous stage and involvement of the hypogastric nerve. Am J Physiol Regul Integr Comp Physiol. 2006;291:R1592–R1601. Ustinova EE, Fraser MO, Pezzone MA Colonic irritation in the rat sensitizes urinary bladder afferents to mechanical and chemical stimuli: an afferent origin of pelvic organ cross-sensitization. Am J Physiol Renal Physiol. 2006;290:1478–1487. Houdeau E., Larauche M., Monnnerie R., Bueno L., Fioramonti J. Uterine motor alterations and estrous cycle disturbances associated with colonic inflammation in the rat. Am J Physiol. 2005;288:630–637. Berkley KJ, Rapkin AJ, Papka RE The pains of endometriosis. Science. 2005;308:1587–1589. Berkley KJ, Dmitrieva N., Curtis KS, Papka RE Innervation of ectopic endometrium in a rat model of endometriosis. Proc Natl Acad Sci U S A. 2004;101:11094–11098. Grummer R. Animal models in endometriosis research. Hum Reprod Update. 2006;12:641–649. Story L., Kennedy S. Animal studies in endometriosis: a review. ILAR J. 2004;45:132–138. Sharpe-Timms KL Using rats as a research model for the study of endometriosis. Ann N Y Acad Sci. 2002;955:318–327. Cason AM, Samuelsen CL, Berkley KJ Estrous changes in vaginal nociception in a rat model of endometriosis. Horm Behav. 2003;44:123–131. Uchiide I., Ihara T., Sugamata M. Pathological evaluation of the rat endometriosis model. Fertil Steril. 2002;78:782–786. Flores I., Rivera E., Ruiz LA, Santiago OI, Vernon MW, Appleyard CB Molecular profiling of experimental endometriosis identified gene expression patterns in common with human disease. Fertil Steril. 2007;87:1180–1199. Author information Authors and Affiliations Corresponding author Additional information This study was supported by S06-GM08239 (to CBA and IF) from the National Institutes of Health (NIH) and by G12-RR03050 (to CBA) from the National Center of Research Resources (NCRR), a component of the NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCRR or NIH. The authors wish to acknowledge the technical assistance of Olga I. Santiago and Lynnette A. Ruiz. We would also like to acknowledge statistical support for this article provided by the Epidemiology and Biostatistics Core Program of the Ponce School of Medicine, federally funded by NIH/NCRR/Research Centers in Minority Institutions (grant 2G12-RR03050). Rights and permissions About this article Cite this article Appleyard, C.B., Cruz, M.L., Rivera, E. et al. Experimental Endometriosis in the Rat Is Correlated With Colonic Motor Function Alterations but Not With Bacterial Load. Reprod. Sci. 14, 815–824 (2007). https://doi.org/10.1177/1933719107309722 Published: Issue date: DOI: https://doi.org/10.1177/1933719107309722