Size Of Endometriotic Lesions Research Articles

Inhibition of CD36-Dependent Phagocytosis by Prostaglandin E 2 Contributes to the Development of Endometriosis

Dysfunction in macrophage-mediated phagocytosis of aberrant cells that undergo retrograde transport to the peritoneal cavity is considered an important factor in the development of endometriosis. However, the mechanisms responsible for the loss of function of macrophages remain largely unknown. Herein, we report that prostaglandin (PG) E(2), via the EP2 receptor-dependent signaling pathway, inhibits the expression of CD36 in peritoneal macrophages, resulting in reduced phagocytic ability. PGE(2)-mediated inhibition of macrophage phagocytic capability was restored by ectopic expression of CD36. Treatment with PGE(2) inhibited CD36-dependent phagocytosis of peritoneal macrophages and increased the number and size of endometriotic lesions in mice. In contrast, blockade of PGE(2) production by cyclooxygenase inhibitors enhanced the phagocytic ability of peritoneal macrophages and reduced endometriotic lesion formation. Taken together, our findings reveal a potential mechanism of immune dysfunction during endometriosis development and may contribute to the design of an effective prevention/treatment regimen.

McGill Pain Questionnaire: A multi‐dimensional verbal scale assessing postoperative changes in pain symptoms associated with severe endometriosis

Objective evaluation of pelvic pain symptoms using a standard pain questionnaire is essential to assessing the treatment of endometriosis and related pain. To evaluate the McGill Pain Questionnaire (MPQ) as a multi-dimensional verbal scale in providing information about chronic pelvic pain associated with endometriosis, before and after laparoscopic surgery. Fifty-five women undergoing laparoscopy for severe endometriosis were asked to complete the MPQ before surgery and at the 6-month follow up. All patients presented with preoperative pain symptoms of variable severity. We obtained the pain indexes and studied their relation with: patients' characteristics (age, body mass index, parity, qualification, occupation); operative findings (number, site and size of endometriotic lesions and presence of pelvic adhesions); and postoperative evolution of variable MPQ pain indexes at the 6-month follow up. Median present pain index (PPI) (index of pain intensity), before surgical treatment was 3 (2-4): preoperative PPI was <2 in 25% of patients while 25% of patients had PPI > 4. Overall median PPI after surgical treatment was 1 (0-2): postoperative index of pain intensity was <1 in 50% of patients, >2 in 25% of patients while 25% of patients did not experience postoperative pain. Overall pain intensity significantly decreased after laparoscopic treatment of endometriosis (Wilcoxon test P < 0.0005). None of the patients' characteristics were found to be significantly correlated with the severity or improvement of preoperative pain at postoperative follow up (P > 0.05), and the intensity of preoperative pain was not correlated to any of the operative variables. There was a significant reduction in all individual MPQ pain indexes; however 18.2% of women did not show improvement of pain symptoms after laparoscopic surgery. An increasing endometrioma diameter was associated with a significant decrease in the difference in evaluative rank score of pain rating index between pain indexes at the 6-month follow up and preoperatively (P = 0.04, Spearman's rank correlation Rho = -0.277). MPQ appears to be useful as a multi-dimensional scale in describing patients' pain semiology and evaluating pain evolution after surgical treatment. However, due to the extreme variability of pain experience, MPQ results don't clarify the relationship between pain intensity and the severity of endometriosis.

Establishment of an improved mouse model of endometriosis allowing the non-invasive assessment of implantation, progression and regression of human endometriotic lesions

Objective: To develop an improved mouse model of endometriosis to allow the non-invasive and dynamic monitoring of human endometriotic lesion implantation and regression. Design: Develop a murine non-invasive experimental model for endometriosis by implanting green fluorescent protein (GFP) expressing fragments of human endometrium into immunocompromised mice. Materials/Methods: We developed an improved, non-invasive animal model for endometriosis. To this end, we introduced the GFP gene into 1–2 mm3 fragments of proliferative phase endometrium, by adenoviral infection in vitro. Ten fragments of GFP-expressing endometrial tissue were then injected either subcutaneously or intra-peritoneally into ovariectomized Nude mice, previously implanted with an estradiol-releasing pellet. Living transplanted mice were periodically examined using a light emitting box allowing GFP excitation. Image analysis allowed quantification of fluorescence intensity and size of endometriotic lesions. In a second set of experiments, monitoring of lesion evolution in untreated or progesterone-treated animals was performed by serial in vivo imaging of animals. Number of lesions, their size and fluorescence intensity, as well as time of complete disappearance were quantified and compared between groups. Results: One day after adenoviral infection, endometrial tissue was shown to be highly fluorescent both by microscopic observation and flow cytometric analysis. GFP-expressing endometrial tissue transplanted to Nude mice was able to form endometriotic lesions. Importantly, fluorescent endometriotic lesions were readily observed non-invasively in subcutaneous and intra-peritoneal sites. Lesion evolution could be followed in the same animal over a 3 week period, and their size and fluorescence intensity could be measured. These two parameters spontaneously decreased with time, likely due to GFP dilution among dividing cells. We postulated that decrease in size and fluorescence intensity of lesions would be more pronounced in mice undergoing endometriosis medication. To make the proof of concept that this model could indeed be used for the pre-clinical testing of new drugs targeting endometriosis, we treated Nude mice exhibiting fluorescent lesions with progesterone. Mice treated with progesterone had a faster and more intense decrease in the number and size of lesions, as assessed by non-invasive imaging. Conclusions: The easier identification of human endometriotic lesions in animals is a major strength of this improved model. Moreover, it allows the visualization of lesion evolution after treatment in the same animal, non-invasively, reducing time, cost and number of animals involved when assessing the efficacy of drugs directed against endometriosis. The dynamic and non-invasive characteristics of this improved mouse model should make it an unprecedented tool for compound evaluation in a pre-clinical setting of endometriosis. Furthermore, this animal model could have many other applications in endometriosis research, such as evaluating the effect of tested genes on lesion implantation and regression. Supported By: PROCREA BioSciences.

Use of a levonorgestrel-releasing intrauterine device in the treatment of rectovaginal endometriosis

Objective: To evaluate the effectiveness of a levonorgestrel-releasing IUD as therapy for endometriosis of the rectovaginal septum. Design: Prospective therapeutic non-randomized, self-controlled clinical trial analyzing changes in pain symptoms and size of lesions induced by the levonorgestrel-releasing IUD over 12 months. Setting: Tertiary referral center for treatment of deep endometriosis. Patient(s): Eleven symptomatic patients with rectovaginal endometriosis. Intervention(s): A levonorgestrel-releasing IUD was inserted and maintained for 12 months. Main Outcome Measure(s): Severity of dysmenorrhea, pelvic pain, and deep dyspareunia were assessed before insertion of the IUD and throughout treatment. The size of rectovaginal endometriotic lesions were evaluated by using transrectal and transvaginal ultrasonography. Result(s): Dysmenorrhea, pelvic pain, and deep dyspareunia greatly improved and the size of the endometriotic lesions was significantly reduced by treatment. Conclusion(s): Insertion of a levonorgestrel-releasing IUD alleviates pain and reduces the size of lesions in patients with endometriosis of the rectovaginal septum.

Effect of prenatal exposure to TCDD on the promotion of endometriotic lesion growth by TCDD in adult female rats and mice.

Several lines of research led to our hypothesis that perinatal exposure to TCDD may alter the sensitivity of adult rodents to the promotional effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on endometriosis. Pregnant rats and mice were treated on gestation day (GD) 8 with either 1 (rats) or 3 (mice) microg TCDD/kg or vehicle. Female offspring were reared to adulthood, and endometriosis was induced surgically. All animals received 0, 3, or 10 microg TCDD/kg 3 weeks prior to surgery, at the time of surgery, and 3, 6, and 9 weeks after surgery. Necropsies were performed 12 weeks after surgery. Measurements at necropsy included the diameter of endometriotic lesions and body, uterine, ovarian and liver weights. While no effect of treatment on lesion diameter was found in rats, analyses revealed that perinatal plus adult exposure to TCDD can increase the size of endometriotic lesions surgically induced in mice. These and additional data on body and organ weights are consistent with previous work. These data confirm the sensitivity of mice to the promotion of endometriotic lesion growth by TCDD and indicate a perinatal effect of TCDD on this parameter when perinatal exposure on GD8 is supplemented with adult exposure to TCDD of female mice.