Loss of lncRNA AK015322 increases sperm morphological abnormalities and impairs motility in mice

Infertility has long been a major health concern worldwide, with male infertility accounting for approximately half of all cases. In recent years, increasing evidence has shown that long non-coding RNAs (lncRNAs) are involved in the regulation of spermatogenesis. LncRNA AK015322 is a testis-specific lncRNA that is highly expressed in testicular tissue. Previous studies have demonstrated that lncRNA AK015322 promotes the proliferation of spermatogonial stem cells (C18-4) in vitro; however, its role in spermatogenesis in vivo remains unclear. To investigate the effects of lncRNA AK015322 gene knockout on spermatogenesis in male mice. LncRNA AK015322 knockout mice (C57BL/6J) were generated using CRISPR/Cas9 technology. Computer-aided sperm analysis was performed to evaluate sperm parameters in knockout mice. In addition, transcriptome sequencing was conducted to identify potential regulatory genes and signaling pathways associated with lncRNA AK015322. Compared with wild-type mice, lncRNA AK015322-deficient mice exhibited delayed epididymal development, increased sperm morphological abnormalities, and significantly reduced sperm motility. Transcriptome sequencing of testicular tissues identified 98 significantly upregulated genes and 109 significantly downregulated genes in knockout mice. Gene ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses indicated that lncRNA AK015322 may be involved in pathways such as the Hippo signaling pathway and androgen response. Differentially expressed genes were further validated by RT-qPCR. LncRNA AK015322 plays an important role in spermatogenesis, and its deletion leads to impaired sperm function and delayed epididymal development in mice.