WTAP-mediated mA modification of Hmgb2 contributes to spermatogenic damage induced by PM exposure.

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