Increased expression of the pluripotency markers sex-determining region Y-box 2 and Nanog homeobox in ovarian endometriosis

Kang

Molecular Reproduction Devel

et al. 2019

Studies have shown that aberrant expression of IL‐12p40, which is encoded by the interleukin‐12B (IL‐12B) gene, may be involved in the development of endometriosis. In this study, we investigated the role of aberrant methylation of the IL‐12B promoter region and its associated expression in the development of ovarian endometriosis. By using pyrosequencing, we analyzed the methylation level of the IL‐12B promoter region in eutopic and ectopic endometrium of patients with ovarian endometriosis and normal endometrium of control women. The expression of IL‐12B mRNA was detected by quantitative real‐time PCR. The results showed that the methylation level of the IL‐12B promoter region in ectopic and eutopic endometrium of patients with ovarian endometriosis was significantly lower than that in endometrium of women without endometriosis ( p < 0.001 and p = 0.041, respectively). In contrast, mRNA levels were significantly increased in ectopic and eutopic endometrium of patients with ovarian endometriosis compared to those in endometrium of women without endometriosis ( p < 0.001 and p = 0.042, respectively). Correlation analysis showed that the methylation level of the IL‐12B promoter region was negatively correlated with mRNA levels of IL‐12B ( p < 0.001). Our data suggested that aberrant methylation of the IL‐12B promoter region may be responsible for aberrant IL‐12B mRNA expression in endometrium tissue of women, which may be associated with the development of ovarian endometriosis in northern Chinese women.

Section: Introductionmentioning

confidence: 99%

Aberrant methylation of the IL‐12B promotor region contributes to the risk of developing ovarian endometriosis

Kang

Molecular Reproduction Devel

et al. 2019

“…In recent years, molecular concepts have been introduced to explain the pathogenesis of endometriosis. It has been reported that aberrant gene expression in endometrium of women may contribute to the etiology of endometriosis [2][3][4][5] .…”

Section: Introductionmentioning

confidence: 99%

Aberrant Methylation of the E-Cadherin Gene Promoter Region in Endometrium and Ovarian Endometriotic Cysts of Patients with Ovarian Endometriosis

An²,

Guan³

et al. 2016

Gynecol Obstet Invest

The loss of E-cadherin expression plays an important role in the development of endometriosis, but the molecular mechanism is not clear to date. It has been confirmed that the hypermethylation of the CpG island may be an important molecular mechanism in the transcriptional inactivation of E-cadherin gene (CDH1) in many cancers. The present study investigated the methylation status of CDH1 promoter region in ovarian endometriotic cysts and the endometrium of women with ovarian endometriosis. The results showed that the frequency of CDH1 promoter methylation in eutopic (26%), ectopic tissues (32%) of women with ovarian endometriosis was significantly higher than that of endometrium tissue of women without endometriosis (8%). Further, results of the study showed that the expression level of mRNA and protein of E-cadherin in methylation-positive tissues was significantly lower than that in methylation-negative tissues (p = 0.023 and 0.035, respectively). Pearson's correlation coefficients analysis showed the level of CDH1 mRNA expression was closely related to the level of E-cadherin protein expression. The results implied that the aberrant methylation of the CDH1 promoter region in the endometrium of the women may contribute, at least in part, to the development of ovarian endometriosis.

“…Thus, the finding of cells displaying germ cell-specific DDX4 and IFITM3 proteins suggests an ovarian origin, and as far as we could track in the literature this is the first evidence reported for ovarian-sourced cells in the endometrioma. In line with this, expression of pluripotency markers such as OCT4 and NANOG and the protoncogene c-KIT in stem-like cells in endometriosis have been described and related to the development of the disease and progression towards ovarian cancer [ 9 , 21 ]. Nevertheless, the presence of ovarian germ line stem cells as contributors to endometriosis progression remains to be further studied through functional analysis in isolated DDX4/IFITM3-positive cells.…”

Section: Discussionmentioning

confidence: 91%

Identification of germ cell-specific VASA and IFITM3 proteins in human ovarian endometriosis

et al. 2015

BackgroundEndometriosis is a gynaecological disorder that affects 6–10 % of female population. It is characterized by the presence of endometrial tissue outside the uterus, most often in the pelvic peritoneum or ovaries. Recent studies have indicated that mesenchymal endometrial stem cells might get involved in endometriosis progression. Although germ line stem cells have been proved to exist in the ovary, their involvement in ovarian endometriosis has not been investigated. In this preliminary report we aimed to identify germinal stem cell markers in ovarian endometriosis.FindingsTen paraffin-embedded ovarian endometriosis samples were screened for germ cell-specific proteins DDX4 (VASA) and IFITM3, and its relation with stem cell marker OCT4, proliferation marker PCNA and estrogen receptor alpha (ESR1), by immunohistochemistry, immunofluorescence and PCR. DDX4 and IFITM3 proteins were expressed in isolated cells and clusters of cells in the cortical region of ovarian endometriotic cysts. DDX4 and IFITM3 co-localized in cells from endometriotic stroma, and DDX4/IFITM3-expressing cells were positive for ESR1, OCT4 and PCNA. No cells expressing neither DDX4 nor IFITM3 were detected in normal endometrial tissue.ConclusionThe identification of germ cell-specific proteins DDX4 and IFITM3 provides the first evidence of ovarian-sourced cells in ovarian endometriotic lesions and opens up new directions towards understanding the still confusing pathogenesis of endometriosis.