Abstract. Endometriosis is a common type of chronic inflammatory disease with an immunological background. In this review, we aimed to explore the contemporary literature on the infection and sterile inflammation that support the pathogenesis of endometriosis. This article reviews the English-language literature on inflammatory, environmental, immunological and oxidative factors associated with endometriosis in an effort to identify factors that cause a predisposition to endometriosis. Intrauterine microbes may be critical for the initiation of endometriosis; the initial activation of pathogen recognition receptors by microbial stimuli results in the activation of proinflammatory pathways and innate immunity. In addition to their response to various exogenous pathogen-associated molecular patterns, Toll-like receptors (TLRs) also recognize a wide range of endogenous danger-associated molecular patterns (DAMPs). The increased expression levels of DAMPs may be involved in the subsequent process of nuclear transcription factor-κB-dependent sterile inflammation. Oxidative stress, secondary to the influx of iron during retrograde menstruation, is involved in the progression of endometriosis. DAMP-mediated danger signals and oxidative stress are bidirectional during sterile inflammation (danger signal spiral). This review supports the hypothesis that there are at least two distinct phases of endometriosis development: The initial wave of TLR activation in modulating innate immune responses would be followed by the second big wave of sterile inflammation.

Abstract. The association between endometriosis and malignant transformation has often been described in the medical literature. A search was conducted between 1966 and 2010 through the English language literature (online Medline PubMed database) using the keywords endometriosis combined with malignant transformation. The search revealed an increase in reports describing endometriosis and malignancy. Approximately 1.0% of women with endometriosis have lesions that undergo malignant transformation. The malignant processes that are associated with endometriosis may be classified into three groups: i) epithelial ovarian cancers (endometrioid adenocarcinoma and clear cell carcinoma), ii) other Müllerian-type tumors, including Müllerian-type mucinous borderline tumor and serous borderline tumor and iii) sarcomas such as adenosarcoma and endometrial stromal sarcoma in the female pelvic cavity. Persistent oxidative stress induced by endometriosis-dependent hemorrhage may be associated with carcinogenesis. In conclusion, the malignant transformation of endometriosis has multiple pathways of development and may share a common pathogenic mechanism; iron-induced oxidative stress derived from repeated hemorrhage.

The histogenesis of endometriosis and endometriosis-associated ovarian cancer is one of the most mysterious aspects of pathology. To better understand the histogenesis of endometriosis and endometriosis-associated ovarian cancer, we analyzed the possibility of a link of endometrium, ovarian surface epithelium, and a cortical inclusion cyst to ovarian endometriosis and endometriosis-associated ovarian cancer by immunohistochemistry using the epithelial membrane antigen (an epithelial marker), calretinin (a mesothelial marker), and hepatocyte nuclear factor (HNF)-1β (a clear cell carcinoma-specific transcription factor). During ovarian surface epithelium invagination, cortical inclusion cyst epithelial cells may, in some cases, undergo mesothelial-epithelial transition and subsequently differentiate into endometriosis. This case of endometriosis that has undergone Müllerian metaplasia arises from the HNF-1β-negative cells. The remaining endometriosis may develop from the late secretory and menstrual endometria, with HNF-1β-positive staining, by retrograde menstruation. Endometrioid adenocarcinoma and clear cell carcinoma arise from the HNF-1β-negative and HNF-1β-positive epithelial cells of endometriosis, respectively. It has been proposed that clear cell and endometrioid-type adenocarcinomas arise from distinct types of endometriosis with different cells of origin.

HNF-1β in endometriosis might be a factor that controls the cell cycle and DNA damage checkpoints.

Abstract. Identification of the potential gene expression profiles of epithelial ovarian cancer and the arrival of newly targeted therapies have advanced the strategies used for treatment of this disease. This review focuses on the design of ongoing and planned clinical trials and offers a synopsis of the Englishlanguage literature for preclinical and clinical targeted therapies for epithelial ovarian cancer. Among many targeted agents, a promising, novel class of targeted drugs for special patient populations expected to improve the effectiveness of current therapy include inhibitors of angiogenesis, poly (ADP ribose) polymerase (PARP) and DNA repair mechanisms. Inhibition of PARP or homologous recombination (HR) repair mediated by Chk1 (checkpoint kinase 1) would selectively sensitize p53 mutation, BRCAness phenotype (serous type ovarian cancer) or HNF (hepatocyte nuclear factor)-1β-overexpressing tumor cells (clear cell type ovarian cancer) to chemotherapeutic agents. The therapeutic response is likely to be limited to a targeted patient, but not to the broad population. This review discusses some of the key current developments and existing challenges.

The aim of the present review was to illustrate how dysregulation of hormonal signaling regulates expressional changes of spatially associated genes in endometriosis. From a multi‑platform endometriosis dataset, an integrated analysis was performed of epigenomic changes of several biologically relevant genes that have been validated in the literature. Estrogen receptor (ER) may act as a direct epigenetic driver for endometriosis establishment, maintenance and progression. A majority of endometriosis susceptibility genes may be present in functional downstream targets of ER and located near the known imprinting genes. Previous studies have shed light on the overlapping genetic signatures between endometriosis development and the defective decidualization process. The steroid hormone‑mediated decidualization signaling pathway was shown to be frequently dysregulated in endometriosis. DNA methylation is associated with various intragenic or intergenic epigenetic modifications of chromatin. Chromatin architecture may be established in temporal and spatial orchestration of the recruitment of genes specifically downregulated in endometriosis. In conclusion, defective chromatin architecture at the ER target locus may have a key role in endometriosis. Endometriosis represents an interesting model to explore the variation of expression of spatially associated genes.

There is now accumulating evidence that endometriosis is a disease associated with an epigenetic disorder. Genomic imprinting is an epigenetic phenomenon known to regulate DNA methylation of either maternal or paternal alleles. We hypothesize that hypermethylated endometriosis-associated genes may be enriched at imprinted gene loci. We sought to determine whether downregulated genes associated with endometriosis susceptibility are associated with chromosomal location of the known paternally and maternally expressed imprinting genes. Gene information has been gathered from National Center for Biotechnology Information database geneimprint.com. Several researchers have identified specific loci with strong DNA methylation in eutopic endometrium and ectopic lesion with endometriosis. Of the 29 hypermethylated genes in endometriosis, 19 genes were located near 45 known imprinted foci. There may be an association of the genomic location between genes specifically downregulated in endometriosis and epigenetically imprinted genes.

Cases of CHMCF following ART may also have higher malignant potential and higher risk of GTD development and become more aggressive biologically. The clinical course of CHMCF after ART seems to be almost the same as that without ART based on the results of literature review.