The role of m6A methylation in female reproductive physiology and pathology

Abstract

N6-methyladenosine (m⁶A) is a critical regulator of female reproductive physiology, yet existing reviews have focused predominantly on oocytes. The objective of this review is to systematically evaluate the regulatory effects of m⁶A throughout the pregnancy process. This review covers aspects such as oocyte maturation, granulosa cell dynamics, endometrial receptivity, immune homeostasis, and systemic adaptations, aiming to demonstrate the comprehensive regulatory capacity of m⁶A in female reproduction. Dysregulated m⁶A modifications in infertility-associated pathologies, including endometriosis, polycystic ovary syndrome, and recurrent miscarriage, are analyzed to identify mechanistic links between an epitranscriptomic imbalance and reproductive dysfunction. The key findings indicate that m⁶A is involved in the entire reproductive process and precisely coordinates stage-specific molecular programs within it, whereas aberrant methylation patterns disrupt gene networks essential for fertility. Notably, m⁶A-modifying enzymes exhibit strong potential as diagnostic biomarkers for female reproductive disorders. The synthesis of the current evidence establishes m⁶A dysregulation as a convergent pathogenic mechanism in diverse infertility etiologies, suggesting that the therapeutic modulation of m⁶A pathways could address unmet clinical needs in reproductive medicine.