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Experimental Intestinal Endometriosis Is Characterized by Increased Levels of Soluble TNFRSF1B and Downregulation of Tnfrsf1a and Tnfrsf1b Gene Expression¹

Departments of Microbiology³ and Physiology,⁴ Ponce School of Medicine, Ponce, Puerto Rico 00732-7004

ABSTRACT

Endometriosis is commonly associated with symptoms similar to those of gastrointestinal diseases, such as inflammatory bowel disease (IBD), leading to erroneous diagnosis and inappropriate management. The role of tumor necrosis factor alpha (TNF) in IBD is well established, but its role in endometriosis—also characterized by the activation of inflammatory mechanisms—is still under study. Furthermore, little is known about the involvement of TNF receptors. Intestinal endometriosis was surgically induced in female Sprague-Dawley rats (n = 10). Control rats (n = 10) received sutures with no implants. Samples of tissue and fluids were collected 60 days after surgery. Endometriotic implants were classified in grades, and the gastrointestinal tract was examined for damage. A significant increase was observed in protein levels of TNF and soluble TNFRSF1B in the peritoneal fluid of experimental rats compared to controls. Expression of Tnf mRNA was significantly increased both in peritoneal leukocytes and in intestinal segments associated with implants in experimental animals. Bioactivity of TNF in tissues was confirmed by overexpression of Icam1, Sele, Vegfa, Flt1 and Kdr. Gene expression of Tnfrsf1a and Tnfrsf1b was downregulated in colon and small intestine of experimental animals, possibly as a mechanism of protection against TNF cytotoxicity. Significant overexpression of genes encoding TNF receptor-associated factors that have been linked to activation of antiapoptotic pathways also was observed. Overexpression of TNF and target genes, underexpression of TNF-receptor genes, and increased shedding of TNFRSF1B in this animal model provide further evidence for involvement of the TNF system in the pathogenesis of endometriosis.

female reproductive tract

¹ Supported by NIGMS F31-GM68392 (C.R.C.) and S06-GM08239 (C.B.A. and I.F.) from the National Institutes of Health. Also supported by RCMI Grant 2 G12 RR03050–18 through the RCMI Publications office and the Molecular Biology Core.

² Correspondence: Idhaliz Flores, Department of Microbiology, Ponce School of Medicine, 395 Zona Ind Reparada 2, Ponce, PR 00716-2347. FAX: 787 290 0876; iflores{at}psm.edu

This article has been cited by other articles:

				C. B. Appleyard, M. L. Cruz, E. Rivera, G. A. Hernandez, and I. Flores Experimental Endometriosis in the Rat Is Correlated With Colonic Motor Function Alterations but Not With Bacterial Load Reproductive Sciences, December 1, 2007; 14(8): 815 - 824. [Abstract] [PDF]