{"paper_id":"5fa21509-b376-45de-b048-1f5d09359de8","body_text":"Abstract\nSyncytin-1 plays a critical role in the maintenance of normal pregnancy by mediating the formation of syncytiotrophoblasts\nthrough a fosugenic action. Encoded by the human endogenous retrovirus envelope gene HERV-W, syncytin-1 trophoblast-specific expression\nis controlled by epigenetic mechanisms. In non-placental tissues, the syncytin-1 gene is suppressed by hypermethylation in the\nLTR promoter region. Hypomethylated and activated syncytin-1 gene is found in placental trophoblast lineages and malignant cells. We\nhere demonstrate that while syncytin-1 gene remains silenced in the eutopic endometrium from endometriotic patients, syncytin-1 mRNA\nand protein are detected in ectopic, endometriotic lesions; particularly the endometrioid glandular endothelial cells. LINE-1 COBRA assay\nand immunohistochemistry using the 5-MC-specific antibody did not detect any changes in global DNA methylation in the endometriotic\ntissues. However, results from COBRA and bisulfite sequencing indicated that the LTR region of the syncytin-1 promoter is\nhypomethylated in endometriotic tissues, highlighting the significance of DNA demethylation in syncytin-1 gene activation. Analysis of\nDNA methyltransferase 3B (DNMT3B) mRNA levels revealed that DNMT3B3, an isoform carrying methyltransferase activity, is downregulated;\nwhereas DNMT3B7, the isoform without enzymatic activity, is upregulated in the endometriotic tissues, pointing to positive\nand negative regulatory functions, respectively, of these isoforms on syncytin-1 methylation. These results have provided the first evidence\nsupporting the involvement of epigenetic mechanisms for syncytin-1 upregulation in endometriotic tissues. Considering recent\nfindings on the nonfusogenic activity of syncytin-1, its expression in endometriotic tissues suggests that this multifunctional protein may\nbe implicated in the pathogenesis and/or progression of endometriosis.\nKeywords: Syncytin-1, HERV-W, DNA methylation, non-fusogenic, DNMT3B isoforms.\n41","source_license":"public-domain-us","license_restricted":false}