Einspanier A, Lieder K, Brüns A, Husen B, Thole H, Simon C
Institute of Physiological Chemistry, Veterinary Faculty, Leipzig, Germany.
Mol Hum Reprod. 2006 May;12(5):291-9. doi: 10.1093/molehr/gal031. Epub 2006 Apr 11.
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, 17betaHSD1 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.
子宫内膜异位症是一种与疼痛和不孕相关的雌激素依赖性妇科疾病，发生于人类和有月经的灵长类动物。在本研究中，绒猴（Callithrix jacchus）作为一种循环雌激素水平高的非月经灵长类动物，首先被用于检验子宫内膜异位症基于子宫内膜脱入腹腔这一假说，其次用于研究由于其雌激素状态导致的子宫内膜异位症发病机制。在2 - 3年的实验期内，通过子宫灌洗对29只雌性绒猴进行盆腔内放置子宫内膜细胞的两种不同实验程序（非侵入性与侵入性）。最早在任何一种处理4个月后，通过彩色多普勒超声在膀胱、子宫和卵巢处检测到首个子宫内膜异位病灶。然而，就诱导的时间进程和产生的子宫内膜异位病灶数量而言，侵入性诱导更有效。通过组织学、免疫组织化学和分子技术对子宫内膜异位病灶进行分析，可将其分为两个不同的组：出现了初始发展阶段，在进一步治疗后导致已确立的子宫内膜异位症的第二阶段。在实验期内，两种程序均显示出子宫内膜异位病灶的血管供应随治疗而增加。侵入性方法更迅速地诱导出子宫内膜异位症的最终确立阶段，并伴有类固醇受体、芳香化酶、17βHSD1和CD10的表达。在我们的子宫内膜反流方案下，总共72%接受治疗的绒猴发生了子宫内膜异位症。我们的数据支持这样一种理论，即通过将子宫内膜脱入腹腔，可以在非月经灵长类动物（绒猴）中人工诱导出子宫内膜异位症。由于绒猴是外周雌激素水平非常高的灵长类动物，这为研究这种雌激素依赖性疾病的发病机制以及对参与类固醇代谢的酶的治疗影响提供了一个有趣的模型。
