Mol. Hum. Reprod. Advance Access originally published online on April 11, 2006
Molecular Human Reproduction 2006 12(5):291-299; doi:10.1093/molehr/gal031
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Induction of endometriosis in the marmoset monkey (Callithrix jacchus)
1Institute of Physiological Chemistry, Veterinary Faculty, Leipzig, 2German Primate Center, Göttingen, 3Institute of Clinical Pharmacology & Toxicology, Charité University Medical School Berlin, Campus Benjamin Franklin, Berlin and 4Solvay Pharmaceuticals Research Laboratories, Hannover, Germany
5 To whom correspondence should be addressed at: Institute of Physiological Chemistry, Veterinary Faculty, An den Tierkliniken 1, Leipzig, Germany. E-mail: einspanier{at}vetmed.uni-leipzig.de
6 Present address: Institute of Physiological Chemistry, Veterinary Faculty, An den Tierkliniken 1, Leipzig, Germany
Endometriosis is an estrogen-dependent gynaecological disease associated with pain and infertility, which occurs in humans and menstruating primates. In this study, the marmoset monkey (Callithrix jacchus), which is a non-menstruating primate with high circulating estrogen levels, was used to test firstly the hypothesis that endometriosis is based on uterine shedding into the peritoneal cavity, secondly to study the pathogenesis of endometriosis due to its estrogenic situation. Female marmoset monkeys (n = 29) were exposed to two different experimental procedures (non-invasive versus invasive) for intrapelvic placement of endometrial cells by uterine flushing over an experimental period of 2–3 years. First endometriotic foci were detected by colour Doppler ultrasound at the bladder, the uterus and the ovaries at the earliest after 4 months of either treatments. However, invasive induction was more effective in terms of the time-course of induction and the number of resulting endometriotic foci. The analysis of the endometriotic foci by histology, immunohistochemistry and molecular techniques allowed a division into two distinct groups: an initial developing stage occurred, which under further treatment led to the second stage of established endometriosis. Both procedures showed a treatment-dependent increase of vascular supply to the endometriotic foci over the experimental period. The invasive method induced the final established stage of endometriosis more rapidly, with the expression of steroid receptors, aromatase, 17ßHSD1 and CD10. Altogether, 72% of the treated marmoset monkeys developed endometriosis under our endometrial reflux protocols. Our data support the theory that endometriosis can be induced artificially in a non-menstruating primate (C. jacchus) by endometrial shedding into the peritoneal cavity. Because the marmoset is a primate with very high peripheral estrogen levels, this offers an interesting model for studying the pathogenesis of this estrogen-dependent disease, as well as for therapeutic impacts on enzymes involved in steroid metabolism.
Key words: CD10/endometriosis/enzymes of steroid metabolism/marmoset monkey/reflux of endometrial cells
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