Epigenetic Dysregulation in Recurrent Pregnancy Loss: The Pivotal Roles of DNMT and TET Enzymes

Recurrent pregnancy loss (RPL) defined as two or more consecutive miscarriages poses significant challenges in reproductive medicine due to its multifactorial etiology including genetic immunologic and environmental factors. Emerging evidence highlights the critical role of epigenetic modifications particularly DNA methylation in RPL. This review explores the involvement of DNA methyltransferase (DNMT۱ DNMT۳A DNMT۳B) and ten-eleven translocation (TET۱ TET۲ TET۳) enzymes in regulating embryonic and placental development. Dysregulation of these enzymes disrupts the balance between methylation and demethylation leading to aberrant gene expression and increased miscarriage risk. Studies demonstrate altered DNMT and TET expression in chorionic and decidual tissues of RPL patients correlating with global hypomethylation or hypermethylation of key developmental genes. Genetic polymorphisms in DNMT and TET genes further elevate RPL susceptibility. Diagnostic approaches including RT-qPCR bisulfite sequencing and methylation microarrays enable precise assessment of epigenetic profiles offering potential biomarkers for early risk prediction. Therapeutically DNMT inhibitors like ۵-azacytidine TET activators such as vitamin C and emerging CRISPR-based epigenetic editing present promising avenues for restoring epigenetic balance though challenges like safety and specificity remain.

کلیدواژه ها:

Recurrent Pregnancy Loss ، Epigenetic ، DNMT ، TET