Dissecting the genetic association between abnormal sperm parameters and depression: a transcriptome-wide analysis of 157 participants.

PURPOSE

Depression often occurs in the males with semen abnormalities. Evidence suggested a genetic correlation between depression and the pathogenesis of abnormal sperm parameters, whereas the mechanisms remained unclear.

METHODS

Genomic datasets of major depressive disorder (MDD) and abnormal sperm parameters were obtained from the Gene Expression Omnibus database. After screening the datasets, differentially expressed genes (DEGs) were identified. GO and pathway enrichment analyses, a protein-protein interaction network, and receiver operator characteristic curve analysis were conducted. Then, MDD-related DEGs (MDRGs), the external validation, immunological, and translational regulation analysis were performed. Moreover, tissue expression of MDRGs was explored.

RESULTS

A total of 249 overlapped MDRGs were discovered in the MDD and abnormal sperm parameters gene sets. MDRGs had a tight relationship with adhesion-associated and PI3 K-Akt-associated biological signaling. The protein-protein interaction module showed the enriched pathways involved in neuron differentiation and cell adhesion. Drug prediction revealed ten pharmacologic candidates. Finally, two hub MDRGs were identified and validated with good diagnostic values. Immunological and translational results showed three closely correlated kinds of CD8 + T lymphocytes, neutrophils, and macrophages, 19 transcription factor-MDRGs, and 71 miRNA-MDRGs interactions. Furthermore, expression signatures of Carnosine Dipeptidase 2 (CNDP2) and Galectin 3 Binding Protein (LGALS3BP) were displayed in cortex and testis.

CONCLUSION

Our study discovered the genetic profiles in abnormal sperm parameters and MDD and elucidated enriched pathways and molecular associations between hub genes and immune infiltration. These findings provide novel insights into the common pathogenesis of both diseases as well as the potential biomarkers for MDD-associated abnormal sperm parameters.