Sperm proteins and cancer-testis antigens are released by the seminiferous tubules in mice and men

Liza O'Donnell, Diane Rebourcet, Laura F. Dagley, Raouda Sgaier, Giuseppe Infusini, Peter J. O'Shaughnessy, Frederic Chalmel, Daniela Fietz, Wolfgang Weidner, Julien M.D. Legrand, Robin M. Hobbs, Robert I. McLachlan, Andrew I. Webb, Adrian Pilatz, Thorsten Diemer, Lee B. Smith, Peter G. Stanton

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12 Citations (Scopus)


Sperm develop from puberty in the seminiferous tubules, inside the blood-testis barrier to prevent their recognition as "non-self" by the immune system, and it is widely assumed that human sperm-specific proteins cannot access the circulatory or immune systems. Sperm-specific proteins aberrantly expressed in cancer, known as cancer-testis antigens (CTAs), are often pursued as cancer biomarkers and therapeutic targets based on the assumption they are neoantigens absent from the circulation in healthy men. Here, we identify a wide range of germ cell-derived and sperm-specific proteins, including multiple CTAs, that are selectively deposited by the Sertoli cells of the adult mouse and human seminiferous tubules into testicular interstitial fluid (TIF) that is "outside" the blood-testis barrier. From TIF, the proteins can access the circulatory- and immune systems. Disruption of spermatogenesis decreases the abundance of these proteins in mouse TIF, and a sperm-specific CTA is significantly decreased in TIF from infertile men, suggesting that exposure of certain CTAs to the immune system could depend on fertility status. The results provide a rationale for the development of blood-based tests useful in the management of male infertility and indicate CTA candidates for cancer immunotherapy and biomarker development that could show sex-specific and male-fertility-related responses.

Original languageEnglish
Article numbere21397
Number of pages18
JournalThe FASEB Journal
Issue number3
Publication statusPublished - Mar 2021


  • biomarker
  • cancer-testis antigen
  • interstitial fluid
  • sperm
  • testis

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