NBMA Promotes Spermatogenesis by Mediating Oct4 Pathway

Abstract

Abstract Non‐obstructive azoospermia is one of the most common causes of male infertility, but there is still no specific treatment drug. Given that the Oct4 (Octamer‐binding transcription factor 4) has an important regulatory effect on spermatogenesis, activating it can effectively promote spermatogenesis, so it is of great value to develop Oct4‐targeted drug design and elucidating its mechanism of action. Here, we screened out the Oct4‐targeted drug molecule NBMA (N‐benzyl‐4‐methoxy‐2‐(1‐(4‐(trifluoromethyl)phenyl)vinyl)aniline) by computer‐assisted technology, and found that it has a significant promoting effect on spermatogenesis in the established mouse azoospermia model. Subsequently, through transcriptome sequencing and enrichment analysis, real‐time fluorescent quantitative PCR (qPCR) and western blot experiments revealed that NBMA promotes the differentiation of spermatogonial stem cells by activating the Oct4 pathway, thereby promoting spermatogenesis. This study proves that NBMA is a molecule with great potential to be developed as a therapeutic drug for azoospermia. It also shows that computer‐assisted, chemical and biological multidisciplinary methods play a very important role in innovative drug discovery.

Keywords

• male infertility
• NBMA
• Oct4
• spermatogenesis
• targeted drug design