Epigenetic dysregulation in differences in sex development.

INTRODUCTION

Sex development is precisely orchestrated by genetic and epigenetic mechanisms; disruption of this intricate process leads to differences in sex development (DSD).

CONTENT: n this review, we systematically examine the role of epigenetic mechanisms in DSD, including DNA methylation, histone modifications, non-coding RNAs, and chromatin remodeling. Unlike previous reviews focused predominantly on animal models, we integrate available epigenetic evidence from human DSD patients and attempt to distinguish causative changes from secondary consequences. Endocrine-disrupting chemicals (EDCs) have been partially validated in animal models to affect gonadal and reproductive functions through epigenetic mechanisms, but human evidence remains limited.

SUMMARY AND OUTLOOK: Finally, we cautiously propose a diagnostic workflow that integrates epigenetic testing and attempt to identify key gaps in current research and suggest testable directions for future studies.