Integrative analysis of GTEx data reveals associations between multi-tissue transcriptomes and human spermatogenic dysfunction

Background: The decline in male sperm production capacity may be related not only to the testes themselves but also may be indirectly influenced by other tissues outside the testes. However, the association between extragonadal tissues and testicular function has not been systematically investigated. Methods: Using the public Genotype-Tissue Expression database (GTEx) bulk RNA-seq dataset, we stratified GTEx subjects into testis functional “good” and “poor” groups based on the expression profiles of spermatogenesis-related genes in testicular tissues. To identify the influence of extragonadal tissues on male fertility, we then compared RNA-seq data of various non-testicular tissues between these two groups. Results: Our findings reveal significant associations between testicular function and the pituitary gland, adrenal gland, lungs, liver, and key brain regions involved in neuroendocrine regulation, including the amygdala, substantia nigra, anterior cingulate cortex, and frontal cortex. Conclusions: These results suggest potential extragonadal pathways that may be associated with male fertility, and provide potential candidate biomarkers for testicular dysfunction diagnosis.

Testis; Spermatogenesis; Extragonadal tissues; Brain regions; Lung; Liver; HPT axis; Adrenal gland

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