GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE311nnn/GSE311763/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311763GEOGSEfalseCcdc117 deficiency triggers compensatory hyperandrogenism to sustain spermatogenesis and male fertilityBackground The precise regulation of testicular steroidogenesis is fundamental to male fertility. While many coiled-coil domain-containing (CCDC) proteins are critical structural components of spermatogenesis, the functional role of the testis-enriched CCDC117 remains undefined, presenting a significant gap in our understanding of local testicular regulation. Methods We generated a Ccdc117 knockout mouse model using CRISPR/Cas9 and characterized the phenotypic consequences through histology, computer-assisted sperm analysis (CASA), and fertility assessments. The molecular underpinnings were investigated via testis-wide RNA sequencing, Western blotting, immunofluorescence, and hormonal measurements. Results Ccdc117ko males developed a paradoxical phenotype: significant testicular hypotrophy alongside completely preserved fertility. Despite a ~25% reduction in testis size, sperm counts, motility, and spermatogenic progression were normal. Transcriptomic analysis uncovered a specific and coordinated upregulation of the steroidogenic pathway, which was validated by a concomitant increase in the protein levels of key enzymes (CYP17A1, StAR, HSD3B2) specifically within Leydig cells. Consequently, serum testosterone levels were significantly elevated by approximately two-fold without a concomitant rise in GnRH.2026/03/31GSE311763GSM9331662GSM9331663GSM9331664GSM9331665GSM9331666GSM933166717021311763Mus musculus