Expression Pattern of Stemness-Related Genes in Human Endometrial and Endometriotic Tissues

Abstract

Endometriosis is a chronic disease characterized by the presence of ectopic endometrial tissue outside of the uterus with mixed traits of benign and malignant pathology. In this study we analyzed in endometrial and endometriotic tissues the differential expression of a panel of genes that are involved in preservation of stemness status and consequently considered as markers of stem cell presence. The expression profiles of a panel of 13 genes (SOX2, SOX15, ERAS, SALL4, OCT4, NANOG, UTF1, DPPA2, BMI1, GDF3, ZFP42, KLF4, TCL1) were analyzed by reverse transcription-polymerase chain reaction in human endometriotic (n = 12) and endometrial samples (n = 14). The expression of SALL4 and OCT4 was further analyzed by immunohistochemical methods. Genes UTF1, TCL1, and ZFP42 showed a trend for higher frequency of expression in endometriosis than in endometrium (P < 0.05 for UTF1), whereas GDF3 showed a higher frequency of expression in endometrial samples. Immunohistochemical analysis revealed that SALL4 was expressed in endometriotic samples but not in endometrium samples, despite the expression of the corresponding mRNA in both the sample groups. This study highlights a differential expression of stemness-related genes in ectopic and eutopic endometrium and suggests a possible role of SALL4-positive cells in the pathogenesis of endometriosis.

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

“…This result differs from that of previous studies [7,9]. The reason may be related to the study population, the ages of the participants, or their menstrual cycles.…”

Interleukin-1β induces cyclooxygenase-2 expression and promotes the invasive ability of human mesenchymal stem cells derived from ovarian endometrioma

“…Endometriosis has been considered as a stem-cell disease, and there is evidence for the existence of stem cells in endometrial tissue (10,23,38). Consistent with this concept, we have previously reported the isolation of EN-MSCs from ectopic and eutopic endometrium (17).…”

“…More recently, clusters of research have inferred the involvement of various factors such as transplantation, genetics (7), immunology (8), environmental exposure, hormones, and endometrium abnormalities (9) in the etiology of this disease. Based on the neoplastic transformation potential of endometriosis into ovarian cancer, the monoclonal origin of endometriotic lesions, and the expression of stemness-related genes in endometriotic tissues, endometriosis has been considered a stem cell-related disease (10)(11)(12)(13).…”

Expression of stem cell-related genes in the endometrium and endometriotic lesions: a pilot study

“…The relationships among sites, stage, and type of endometriotic implants, as well as the differences between superficial and deep endometriosis have not been well characterized and are controversial [ patterns of endometriosis have been analyzed in many studies to identify differentially expressed genes and to explore the potential molecular mechanisms involved in development of endometriosis [39][40][41][42][43][44].…”

“…Most of these genes are related to stem cell physiology [39][40][41][42][43][44]. Therefore, these data suggest high activity of these cells in endometriotic lesions.…”