Amyloid/RNA Condensates with Germ Granule Characteristics Are Present in Rat Epididymal Spermatozoa and Exhibit Prion-Like Propagation Activity

Environmental exposures to the germline can alter its epigenome resulting in new traits being acquired by offspring. While the epigenetic carrier in mammalian spermatozoa remains unknown, studies in C.elegans show that amyloids and sperm-specific populations of germ granules, phase-separated biomolecular condensates enriched in RNA-binding proteins and small noncoding RNAs, transmit heritable epigenetic phenotypes to descendant cells. Here we discovered that rat epididymal spermatozoa contain germ granule-like condensates in the head perforatorium, a cytoplasmic derived structure that participates in early post-fertilization events. The perforatoria condensates contain evolutionarily conserved germ granule markers and small noncoding RNAs and are enriched in amyloid, including those of the clinically relevant amyloidogenic proteins androgen receptor (AR) and TDP43. Further, perforatoria extracts exhibit prion-like propagation behavior by functioning as molecular seeds to template amyloid assembly in recombinant AR and TDP43. We propose that nature has conserved sperm germ granule-like structures throughout evolution to allow an organism to respond and adapt to a changed environment by passing environmentally encoded information to the embryo via a non-Mendelian protein-based mechanism of inheritance.