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Problem How are the effects of Tokishakuyakusan (TSS), a traditional Japanese medicine (Kampo) on murine endometriosis model? Methods BALB/c mice were used for making the murine endometriosis model. Homogeneous uterus was surgically implanted with lipopolysaccharide (LPS) in peritoneal cavity. We administered 2 weeks of TSS (1.0 g/kg) orally. Upon treatment completion, we performed the hot plate test for all mice and collected blood samples before sacrifice. Then, the endometriosis-like lesions and uteri in the abdominal cavity were harvested. Concentrations of several cytokines in sera and cyst fluids were measured using Bio-Plex Suspension Array System. IL-33 localization was determined by immunohistochemistry. Gene expression of inflammatory cytokines in the endometriosis-like lesions or the eutopic endometrium was evaluated by real-time RT-PCR. Results After 14 days of TSS treatment, the numbers of endometriosis-like cysts and cyst weight were significantly decreased. In TSS-treated mice, the latency against heat stimuli was extended. Inflammatory cytokine concentrations in sera were not changed by TSS treatment. TSS intake decreased IL-33 mRNA expression in endometriosis-like lesions and led to the tendency of attenuation of the elevated IL-33 synthesis in the cyst fluids of lesions. Conclusion These results suggest the TSS ameliorated the hyperalgesia and lesion formation on the LPS-accelerated endometriosis-like model. TSS represents a possible ideal target of novel therapeutics for endometriosis patients with dysmenorrhea.

Endometriosis results from the aberrant growth of endometrium outside the inner lining of the uterine cavity. Similar to humans, the primates also menstruate and hence, the primate models constitute the gold standard for studying the pathogenesis and potential treatment for this disabling disease in women. Due to the expense in carrying endometriosis research in primates, other models have been developed for understanding the pathobiology and potential treatment of endometriosis. This includes explanting human endometrial tissues in athymic nude mice or using homologous mouse models. Here, we examine the murine models of endometriosis, the impact of forced induced inflammation on its development, similarities in the gene expression profile in the endometriotic tissues in such models with that seen in human endometriosis, and the drugs that are being used in such models as potential new treatment for endometriosis.

Problem To evaluate the effects of SR-16234 (SR), a selective estrogen receptor modulator (SERM), on murine endometriosis-like lesions. Method of study BALB/c mice (n = 53) were used to establish the murine endometriosis model. Ovariectomized, estradiol replaced, 6-week-old murine endometriosis model were injected with lipopolysaccharide (LPS) with or without SR (1 mg/kg/d) or vehicle, over a period of 4 weeks. Upon treatment completion, the endometriosis-like lesions that developed in the abdominal cavity of mice were counted, measured, and collected. Gene expression of inflammatory cytokines and estrogen receptor (ER) in the lesions was assessed by real-time RT-PCR. Immunohistochemical analysis was used to evaluate the effect of SR on cell proliferation, angiogenic activity, inflammation, and NF-κB phosphorylation. Results Treatment with SR significantly reduced the total number and size of lesions per mouse without inducing endometrial growth. In addition, SR downregulated LPS-enhanced Vegf, Il-6, Ptgs-2, and Ccl-2 and ER mRNA expression in endometriosis-like lesions. Immunohistochemical analysis demonstrated a decrease in percentage of positive cells of Ki67, and intensity and rate of positive cells of ERα, CD3, F4/80, PECAM by SR treatment. SR also decreased the expression of NF-κB p65 and phospho-NF-κB p65. Conclusion SR has a regressive effect on the development of murine endometriosis-like lesions.

Until recently, adenomyosis has been associated with multiparity, not impaired fertility. Currently, adenomyosis is diagnosed with increasing frequency in infertile patients since women delay their first pregnancy until their late 30s or early 40s. Although an association between adenomyosis and infertility has not been fully established, based on the available information, recent studies suggested that adenomyosis has a negative impact on female fertility. Several uncontrolled studies with limited data also suggested that treatment of adenomyosis may improve fertility. This article discusses (i) the hypothesis and epidemiology of adenomyosis, (ii) diagnostic techniques, (iii) clinical evidence of correlation between adenomyosis and infertility, (iv) proposed mechanism of infertility in women with adenomyosis, (v) different treatment strategies and reproductive outcomes, and (vi) assisted reproductive technology outcome in women with adenomyosis. Target Audience Obstetricians and gynecologists, family physicians. Learning Objectives After completing this activity, the learner should be better able to: Recall the hypothesis and epidemiology of adenomyosis; Evaluate the important findings on improved imaging techniques to diagnose adenomyosis; Understand that the presence of adenomyosis may impair the reproductive outcomes in women with adenomyosis; Explain the proposed mechanism of infertility in women with adenomyosis; Give the most appropriate treatment for better reproductive outcomes in women with adenomyosis; and Advise patients that surgery could be effective in women with adenomyosis with a history of IVF failure although latter finding could be partly attributed to the higher rate of early miscarriage.

Endometriosis is a common chronic benign disease that affects reproductive age women and causes chronic pelvic pain and infertility. Despite its prevalence, the exact mechanisms of the pathogenesis of endometriosis-associated infertility are unknown, and precise standards of management have not yet been established. Medical and surgical treatments for endometriosis have different effects on the chance of conception, either spontaneously or via assisted reproductive technologies (ART). In this manuscript, we review the literature from years 1979 to 2015 to report on the proposed mechanism of endometriosis-associated infertility, the staging system of endometriosis for pregnancy outcomes and the current management of patients with endometriosis-associated infertility.

Problem Is lipopolysaccharide (LPS) involved in the development of endometriosis? Method of Study BALB/c mice (n=69) were used for the murine endometriosis model. Mice with surgically induced endometriosis were injected with LPS intraperitoneally. After 4 weeks of LPS injections with or without the nuclear factor-kappa B (NF-κB) inhibitor, the extent of endometriosis-like lesions was evaluated. Expression of inflammatory factors in the implants was evaluated using real-time RT-PCR. Cell proliferation, angiogenic activity, inflammation, and NF-κB phosphorylation were assessed by immunohistochemical staining. Results Lipopolysaccharide increased total number, size, and mRNA expression of Ptgs-2, Vegf, Ccl-2, and Il-6 in endometriosis-like lesions. LPS also increased the percentage of Ki67-positive cells and enhanced the intensity and rate of positive cells of CD3, F4/80, and PECAM. Intense expression of phospho-NF-κB p65 after LPS administration was observed. Treatment with the NF-kB inhibitor negated these LPS-induced effects. Conclusions LPS-induced pelvic inflammation status enhanced the development of murine endometriosis-like lesions via NF-κB pathway.