WTAP-mediated m⁶A modification of Hmgb2 contributes to spermatogenic damage induced by PM_2.5 exposure

N⁶-methyladenosine (m⁶A) is extensively involved in complex spermatogenesis while being extremely sensitive to environmental exposure. Numerous studies have revealed the toxicity of fine particulate matter (PM_2.5) to the male reproductive system, but the specific epigenetic mechanisms involved have been underexplored. Here, we investigated the effect of m⁶A modification on PM_2.5-induced male reproductive impairment by establishing a real-time PM_2.5-exposed mouse model and a GC-2spd cell model. PM_2.5 exposure resulted in damage to the spermatogenic epithelium and mitochondrial abnormalities in spermatocytes and significantly reduced sperm motility in mice. Gene enrichment analyses of testicular tissue differential m⁶A modified genes were significantly enriched to spermatogenesis in the PM_2.5-treated mice compared with the control group, and the expression of the methylase WTAP was markedly decreased after PM_2.5 exposure. Moreover, PM_2.5 exposure resulted in a significant reduction in the expression of the spermatogenesis-related gene Hmgb2, as well as in the level of the Hmgb2 m⁶A modification. Transcriptome sequencing and verification experiments suggested that Hmgb2 may regulate spermatocyte ATP levels. In addition, we demonstrated that the m⁶A methylase WTAP affects Hmgb2 mRNA stability via m⁶A modification. Our study provides new insights into PM_2.5-induced damage to spermatogenesis and reduced sperm motility.