Sperm proteins and cancer-testis antigens are released by the seminiferous tubules in mice and men
Details
Publication Year 2021-03, Volume 35, Issue #3, Page e21397
Journal Title
FASEB Journal
Abstract
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.
Publisher
Wiley
Keywords
biomarker; cancer-testis antigen; interstitial fluid; sperm; testis
WEHI Research Division(s)
Advanced Technology And Biology
PubMed ID
33565176
Open Access at Publisher's Site
https://doi.org/10.1096/fj.202002484R
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2021-03-09 01:36:57
Last Modified: 2021-03-09 02:41:12
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