New insights into the potential mechanisms of spermatogenic failure in patients with idiopathic azoospermia.

: Idiopathic azoospermia (IA) refers to azoospermia without a clear etiology. Due to the unclear etiology and pathological mechanism of IA, there is no effective treatment for IA. The development of assisted reproductive and microsperm extraction technologies has brought hope to IA patients with fertility problems. However, there are still many IA patients whose testes lack healthy sperm, causing infertility. Therefore, it is key to identify how testicular spermatogenic failure can be reversed to promote spermatogenesis in patients with IA to resolve fertility problems; these goals are a great challenge in reproductive medicine. The underlying genetic factors seem to be important pathological factors of IA. Understanding the role of genetic factors in the pathological mechanism of spermatogenic failure in IA patients is of great value for future studies and treatments and is also an important reference for the reproductive health of males and their offspring. A method combining sequencing technology and bioinformatics analysis is an important means to understand the genetic pathological mechanisms. We used bioinformatics analysis to study the public human IA dataset. We found that the pathogenic mechanism of IA may be related to abnormal ciliary structure and function and disrupted RNA metabolism in spermatogenic cells. Disrupted m6A regulation of spermatogenesis may be an important pathological mechanism of IA and warrants attention. Finally, we screened for key genes and potential therapeutic drugs to determine future research directions.