The epididymal amyloid matrix: structure and putative functions

BACKGROUND: We previously demonstrated the normal mouse epididymal lumen contains a non-pathological amyloid matrix that surrounds spermatozoa and plays important roles in sperm maturation and protection. OBJECTIVE: The objective herein was to present a review of this work, including studies showing the amyloid structures of four members of the CRES (cystatin-related epididymal spermatogenic) subgroup are integral and essential components of the amyloid matrix. METHODS: We used conformation-dependent reagents that recognize the cross-β-sheet structure characteristic of amyloid, including thioflavin S (ThS), thioflavin T (ThT), anti-amyloid antibodies, and X-ray diffraction, as well as negative-stain transmission electron microscopy (TEM) to visualize amyloid structures in the epididymal lumen. Antibodies that specifically detect each CRES subgroup family member were also used in indirect immunofluorescence analysis. RESULTS AND DISCUSSION: The epididymal lumen contains an amyloid matrix that surrounds maturing spermatozoa and represents a functional amyloid. Alterations in the structure of the amyloid matrix by the loss of the CRES subgroup members or the overexpression of cystatin C result in epididymal pathologies, including infertility. Preliminary data suggest the epididymal amyloid matrix is structurally and functionally similar to bacterial biofilms. CONCLUSION: Together, these results suggest the amyloid matrix serves important roles in epididymal function including sperm maturation and protection.