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This Article Full Text Full Text (PDF) All Versions of this Article: 74/1/131    most recent biolreprod.105.043349v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by D'Hooghe, T. M Articles by Mwenda, J. M. Search for Related Content PubMed PubMed Citation Articles by D'Hooghe, T. M Articles by Mwenda, J. M. Agricola Articles by D'Hooghe, T. M Articles by Mwenda, J. M.

Recombinant Human TNFRSF1A (r-hTBP1) Inhibits the Development of Endometriosis in Baboons: A Prospective, Randomized, Placebo- and Drug-Controlled Study¹

Leuven University Fertility Center,⁴ Department of Obstetrics and Gynecology, University Hospital Gasthuisberg, 3000 Leuven, Belgium Serono Reproductive Biology Institute,⁵ Rockland, Massachusetts 02370 Institute of Primate Research,⁶ 00502 Karen-Nairobi, Kenya

ABSTRACT

Endometriosis is associated with chronic inflammation, including an increased macrophage activity with increased secretion of cytokines, such as tumor necrosis factor (TNF) or TNF superfamily member 2, previously known as TNF. In the present study, we tested the hypothesis that recombinant human TNFRSF1A (r-hTBP1) can inhibit the development of endometriotic lesions in the baboon, an established model for the study of endometriosis. Endometriosis was induced using intrapelvic injection of menstrual endometrium in 20 baboons with a normal pelvis. In the first part of the study, 14 baboons were randomly assigned to subcutaneous treatment with r-hTBP1, placebo, or GnRH antagonist (positive control). In the second part of the study, menstrual endometrium from 6 baboons was randomly incubated with either PBS or r-hTBP1 before intrapelvic seeding. Video laparoscopy was performed 25 days later to document the number, surface area, and estimated volume of endometriotic lesions and adhesions; to calculate the revised American Fertility Society (rAFS) score and stage; and to confirm the histological presence of endometriosis. In the first part, baboons treated with r-hTBP1 or with Antide (Bachem) had a lower endometriosis rAFS score, a lower surface area and estimated volume of peritoneal endometriotic lesions, and a lower histological confirmation rate compared with controls. Because of less adnexal and cul-de-sac adhesions, the number of baboons with endometriosis of stage II, III, or IV was lower among baboons treated with r-hTBP1 or Antide than among controls. In the second part, the surface area of endometriotic lesions was lower, and less severe endometriosis was observed in r-hTBP1-treated baboons. No hypoestrogenic effects were observed in baboons treated with r-hTBP1. In conclusion, r-hTBP1 can effectively inhibit the development of endometriosis without hypoestrogenic effects in baboons.

cytokines, gonadotropin-releasing hormone, immunology, ovulation, steroid hormones

¹ Supported by Serono, Inc. (Geneva, Switzerland). T.M.D'H. was sponsored by the Belgian Fund for Scientific Research and the Leuven University Research Council.

² Correspondence: Thomas M. D'Hooghe, Leuven University Fertility Center, Dept. of Ob/Gyn, University Hospital Gasthuisberg, B3000 Leuven, Belgium. FAX: 32 16 343607; thomas.dhooghe{at}uz.kuleuven.ac.be

³ These authors contributed equally to this work.