Single-Cell Transcriptomics Reveals Immune Activation and Spermatogenic Disruption in the Prostate Cancer-Associated Testis

Prostate cancer is one of the most prevalent cancers among men. Androgen plays a crucial role in promoting the growth of normal and abnormal prostate, and the testicles are the primary source of androgen production. The interplay between the testicles and the prostate partially determines the progression of prostate cancer. However, the precise role of testicular tissue in the initiation and progression of prostate cancer remains unclear. We established a single-cell transcription atlas of testicle tissue from healthy older adults and prostate cancer (PCa) IV stage patient. In total, 52,686 cells from the testis tissues of the older group and PCa patient group were obtained and annotated. We found that the testis of PCa patients lacked a cluster of cells which related to cell adhesion molecules. PCa can lead to an increase in the proportion of round sperm in germ cells, as well as the upregulation of certain immune-related genes that are highly expressed in round sperm. Notably, unique cell populations have been identified in immune cells and testicular peritubular cells (TPCs). The immune cells, germ cells, leydig cells and TPCs all have certain immune responses. In addition, spermatogenic genes are highly expressed in TPCs and sertoli cells of Pca group, likely due to the abnormal androgen secretion in PCa patients. Our study discovered the PCa patient specific testis characteristics at single cell resolution and suggested the adverse reproductive effects for the PCa population.