Daniel Chai | PubMed Health

PubMed2003

Steroid receptor and aromatase expression in baboon endometriotic lesions.

OBJECTIVE: To evaluate steroid receptor and aromatase gene expression in endometriotic lesions, and determine the effects of endometriosis on uterine receptivity in a baboon model for endometriosis. DESIGN: Prospective study to determine the expression of steroid receptors, and aromatase in ectopic endometriotic lesions and endometrial genes in the eutopic endometrium of baboons with induced endometriosis by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunocytochemistry. SETTING: University research laboratory and primate research facility. ANIMAL(S): Normally cycling baboons inoculated intraperitoneally with menstrual endometrium to induce endometriosis. INTERVENTION(S): Endometriotic lesions were resected during laparotomy, and endometrium was obtained by endometrectomy or after hysterectomy. MAIN OUTCOME MEASURE(S): Steroid receptor and aromatase expression by RT-PCR and immunocytochemistry in endometriotic lesions and glycodelin and alpha-smooth muscle actin expression and localization in endometrium after chorionic gonadotropin (CG) stimulation. RESULT(S): This study demonstrated that estrogen receptor-alpha (ERalpha) and progesterone receptor (PR) were expressed in both ectopic and eutopic endometrium between 1 and 10 months after inoculation. In contrast, ERbeta was only expressed in the ectopic endometriotic lesions. Aromatase expression was only evident in lesions obtained 10 months after inoculation. Infusion of CG during the luteal phase failed to induce the expression of glycodelin in the glandular epithelium or alpha-smooth muscle actin (alpha-SMA) in stromal cells in animals with endometriosis as early as 1 and 4 months after inoculation. CONCLUSION(S): The ERbeta expression is selectively up-regulated in the endometriotic lesions at all stages of the disease, whereas aromatase expression is not evident until the disease progresses. However, expression of uterine receptivity markers was down-regulated as early as 1 and 4 months after inoculation.

Actins↗

PubMed2002

A modified baboon model for endometriosis.

Endometriosis is one of the most common causes of infertility and chronic pelvic pain and affects 1 in 10 women in the reproductive-age group. Although existence of this disease has been known for over 100 years, our current knowledge of its pathogenesis, the pathophysiology of related infertility, and its spontaneous evolution is limited. Several reasons contribute to our lack of knowledge, the most critical being the difficulty in carrying out objective long-term studies in women. Thus, we and others have developed the baboon as an appropriate nonhuman primate to study the etiology of this disease. We suggested that endometriosis develops in two distinct phases. Phase I is invasive and dependent on ovarian steroids. Phase II, which is the active phase of the disease, is characterized by endogenous estrogen biosynthesis. Following inoculation with menstrual endometrial tissues in two consecutive menstrual cycles, baboons develop lesions that are similar to those seen in humans. Laparoscopy at 1, 4, and 10 months revealed a preponderance of red raised nodules at the first month, while both red lesions and reddish-blue proliferative endometriotic lesions were evident at 4 and 10 months. The presence of glandular tissue and stromal fibroblasts in these lesions was confirmed by histology. Lesions obtained at 1 and 4 months expressed estrogen receptor beta (ERbeta), matrix metalloproteinase-7 (MMP-7), and vascular endothelial growth factor (VEGF) predominantly. However, aromatase expression was only readily evident at 10 months, although some lesions obtained at 4 months expressed low levels of aromatase. Therefore, our preliminary data suggest that endometriosis can be artificially induced in baboons, and the role of exogenous and endogenous estradiol in proliferation, angiogenesis, and immune modulations can now be evaluated in a potentially systemic manner.

Animals↗