RNA N6-methyladenosine modification, spermatogenesis, and human male infertility

RNA N6-methyladenosine (m6A) modification is one of the main forms of posttranscriptional modification, and its dysregulation is involved in a series of pathological processes. RNA m6A regulators, which mediate dynamic RNA m6A modification, are expressed in almost all types of testicular cells, including spermatogenetic cells and somatic cells. Cumulative studies have found that knockout of RNA m6A regulators in the testis leads to abnormal metabolism of the target mRNAs, which eventually causes spermatogenetic disorders and infertility. To date, a role for dysregulated RNA m6A modification in human male infertility remains elusive; however, dysregulated expression of RNA m6A regulators in abnormal human semen samples, including oligospermia, asthenozoospermia and azoospermia, has been found. Therefore, we speculate that abnormal RNA m6A methylation may be an important mechanism of male infertility. In this review, we summarize the recent findings regarding the spatiotemporal expression of RNA m6A regulators in the testes, mechanisms of RNA m6A modification in spermatogenesis and the relation between dysregulated RNA m6A regulators and human male infertility. In addition, we also discuss future directions in studying the molecular mechanism of male infertility and exploring their clinical applications from the viewpoint of RNA m6A modification.