Human circBOULE RNAs as potential biomarkers for sperm quality and male infertility

Reliable molecular biomarkers to predict fertility remain scarce. The current study investigated the potential of testis-specific circBOULE RNAs as biomarkers for male infertility and sperm quality. Using reverse transcription-PCR and real-time reverse transcription-PCR assays, we identified seven circular RNAs from the human BOULE gene in human sperm. We observed that the expression level of circEx3-6 was significantly reduced in asthenozoospermia, while the expression levels of both circEx2-6 and circEx2-7 were decreased in teratozoospermia, compared with the controls. Furthermore, we demonstrated that the expression level of circEx2-6 was negatively correlated with the sperm DNA fragmentation index, and the expression level of circEx2-7 was correlated with both fertilization and cleavage rates in those treated with the assisted reproductive technologies. Further functional analyses in a transgenic fly model supported the roles of circBOULE RNAs in sperm development and human male fertility. Collectively, our findings support that sperm circBOULE RNAs may serve as diagnostic biomarkers for assessing sperm motility and DNA quality. Therefore, clinical application and significance of sperm circBOULE RNAs in the assisted reproductive technologies warrant further investigation.