Unraveling the epigenetic landscape: m6A modifications in spermatogenesis and their implications for azoospermia

N6-methyladenosine (m6A) RNA modifications have emerged as crucial epigenetic regulators in various biological processes, including spermatogenesis. This review aims to elucidate the role of m6A modifications in spermatogenesis and their implications for male infertility, particularly non-obstructive azoospermia (NOA). We conducted a comprehensive review of recent studies focusing on m6A methyltransferases, demethylases, and reader proteins involved in spermatogenesis. Our analysis reveals that m6A modifications play a vital role in regulating mRNA stability, translation efficiency, RNA splicing, and RNA–protein interactions during spermatogenesis. Key m6A regulators such as METTL3, METTL14, ALKBH5, and YTHDF proteins are critical for proper spermatogenic function. Abnormalities in these regulators, due to genetic mutations, expression dysregulation, or environmental factors, are linked to impaired spermatogenesis and NOA. Studies also indicate significant dysregulation of m6A-related genes in NOA patients, suggesting a potential diagnostic and therapeutic target for male infertility. m6A modifications are integral to the regulation of spermatogenesis and male fertility. Further research is needed to fully understand the mechanisms by which m6A modifications influence spermatogenesis and to explore potential therapeutic interventions. This review highlights the importance of m6A modifications in male reproductive health and underscores the need for continued investigation in this emerging field.