Exploring the epigenetic mechanisms of recurrent pregnancy loss: from genetic predisposition to environmental influences.

Recurrent pregnancy loss (RPL) is a complex and emotionally distressing condition defined by the occurrence of two or more consecutive miscarriages before 20 weeks of gestation. The exact causes of RPL remain unclear, despite extensive research into its genetic, immune, and environmental underpinnings. Recent advances in epigenetics have revealed that alterations in DNA methylation, histone modifications, and non-coding RNA expression play crucial roles in regulating pregnancy-related processes such as immune tolerance, placental development, and embryo implantation. These epigenetic changes are influenced not only by genetic predisposition but also by environmental factors, highlighting the dynamic interaction between genes and the environment in the pathogenesis of RPL. This review explores the role of epigenetics in RPL, focusing on the identification of epigenetic biomarkers, their potential for early diagnosis and prediction, and their implications for targeted therapeutic interventions. We also discuss how environmental factors, including diet, stress, and pollutants, can modify epigenetic regulation, potentially increasing the risk of RPL. Furthermore, emerging epigenetic-based therapies, such as epigenetic drugs and gene editing, are discussed as potential approaches to improving pregnancy outcomes in women with RPL. This review underscores the need for further research to translate epigenetic findings into clinical applications for personalized and precision medicine in RPL management.