Effect of inflammatory environment on development of endometriosis in murine model

Endometriosis is associated with intraperitoneal and systemic inflammatory environments. However, it is not clear whether inflammation is induced by endometriosis or whether inflammation predisposes the development of endometriosis. This study evaluated the effect of pre-exposure to an inflammatory stimulus on the risk of development of endometriosis in a murine model of this disease. In vivo study. C57BL6 mice (n=17) underwent oophorectomy and received slow-release estradiol via silastic implants 24 hour prior to random assignment to the phosphate buffered saline (PBS) group (n=9; PBS intraperitoneal injections daily for 7 days) or to the lipopolysaccharide (LPS) group (n=8, LPS 1.5 mg/kg intraperitoneal injections daily for 7 days). Subsequently, all animals received intraperitoneal injections of minced uterine tissues from Green Fluorescent Protein-positive (GFP+) donor mice euthanized 24 hour after oophorectomy and placement of estradiol implants. Recipient animals were euthanized 2 weeks after receiving the minced uterine tissue. Using ultraviolet light, endometriotic lesions were identified and excised. Number, size and location of endometriotic implants were compared between the LPS and PBS groups. Histologic assessment of lesions was performed following hematoxylin & eosin staining to verify the presence of endometrial glands and stroma. Wilcoxon rank sum test was used to compare the number and volume of lesions; P<0.05 was considered statistically significant. Endometriotic lesions were found in all eight mice pre-exposed to LPS but in only four of nine mice that received PBS (P=0.03, Fisher’s exact test). Administration of LPS prior to induction of endometriosis also significantly increased the total number of endometriotic lesions per mouse in comparison to PBS (1.7±0.2 vs. 0.4±0.2; P=0.004, respectively). Total volume of lesions per mouse ranged from 1.5 to 175 mm3 in the LPS group and from 0 to 87 mm3 in the PBS group; this difference was significant with the mean (±SEM) in the LPS and PBS groups of 61±16 mm3 vs. 14.7±15 mm3, P=0.01, respectively. Histologic examination confirmed the uterine origin of the endometriotic lesions. Pre-exposure of mice to an inflammatory stimulus within the peritoneal cavity subsequently promoted the attachment and growth of endometriotic lesions. This finding suggests that biologic drivers of peritoneal inflammation may increase an individual’s risk for the development of endometriosis. In turn, therapeutic strategies focused on reducing peritoneal inflammation may be effective in limiting the development, progression or recurrence of endometriosis.