Even though the epididymal environment actively promotes sperm survival, the presence
of the nonviable sperm population in this region has been observed in many species.
Degenerating spermatozoa release enzymes or antigens that could have a detrimental
effect on the viability of the neighboring cells. It may be a source of autoantigens that
could induce the immune response if they can escape from the blood-epididymis barrier.
Anti-sperm antibodies are not uncommon in men; they develop for reasons that are not
understood, and they are a source of infertility that is difficult to correct. What are the
protective strategies of the epididymis that could prevent these negative impacts on
male fertility? We identified a hamster epididymal secretory protein of 64kDa (originally
termed HEF64) which assembles into 260 and 280kDa disulfide-linked oligomers.
HEF64 is secreted by principal cells of the cauda epididymidis and specifically binds to
and then polymerizes into a proteinaceous “death cocoon” coating defective
spermatozoa and sperm fragments. The 260/280 kDa oligomers are termed eFGL (for
epididymal fibrinogen-like oligomer). Biochemical studies revealed that eFGL is
composed of two subunits; the 64kDa polypeptide identified as fibrinogen-like protein-2
and the 33kDa polypeptide identified as fibrinogen-like protein-1. Our morphological
studies demonstrated that the eFGL is polymerized into a cocoon-like complex, masking
defective luminal spermatozoa and sperm fragments, not the viable sperm population.
This research project will define the biochemical basis of this secretory protein (eFGL)
recognition and its biological effects on the defective spermatozoa. Our hypothesis is
that eFGL represents a novel and unique mechanism to shield the viable sperm
population and/or the epididymal epithelium from degenerating spermatozoa contained
within the tubule lumen. Completion of the proposed studies will provide new insights
into the mechanisms by which the potentially unique epididymal protein functions in the
recognition and elimination of defective spermatozoa. Direct demonstration of
epididymal protein function would seem critical for development of strategies to help
infertile males with normal sperm production but low “sperm quality” of the ejaculate.
The aims of this project are: 1. To identify which organelles and potential ligands of
defective spermatozoa bind the epididymal eFGL 2. To determine if eFGL binding to
specific sperm ligands promotes sperm death and/or death cocoon polymerization.