JAGGED1 modulates bull spermatozoa acrosome reaction and fertilization

To acquire fertilizing ability, mammalian spermatozoa (SPZ) must undergo acrosome reaction, which is associated to protein remodeling and relocation. Previous studies showed that Notch ligand JAGGED1 is relocated from the apical to post-equatorial segment of bull SPZ during acrosome reaction. This study evaluated the effects of JAGGED1 supplementation or functional inhibition on bull SPZ acrosome reaction, and subsequent fertilization and embryo development rates. Swim-up derived SPZ was treated with JAGGED1 (10, 50, or 100 ng/mL) or anti-JAGGED1 antibody (7.5 µg/mL). Treatment with JAGGED1 reduced the proportion of SPZ with non-reacted acrosome during the spontaneous acrosome reaction (44% vs 10.8% at 50 ng/mL; p < 0.001) and increased the proportion of acrosome-reacted SPZ (24.5% vs. 34.6% at 100 ng/mL; p < 0.001) during the induced acrosome reaction with calcium ionophore. Treatment with anti-JAGGED1 antibody lowered the proportion of acrosome-reacted SPZ (39.1% vs. 26.1%; p < 0.0001) during the induced acrosome reaction and decreased the fertilization rate (69.7% vs. 54.8%; p < 0.0001). Overall, results indicate that JAGGED1 accelerates the SPZ acrosome reaction, thus limiting the timespan of fertilization ability. It is hypothesized that JAGGED1 contributes to SPZ cytoskeleton remodeling, interacting with other proteins. Lay summary: To successfully fertilize an egg, mammalian sperm must go through a series of final changes. These changes involve adjustments and the movement of important proteins within the spermatozoa head. This study examines how a protein called JAGGED1 moves within the bull spermatozoa head as it gets ready to fertilize an egg. When extra protein was added, more sperm were able to complete the final change needed for fertilization. When the sperm's own JAGGED1 was blocked, fewer completed this change, and fertilization was less successful. Together, these results show that JAGGED1 helps spermatozoa get ready to fertilize an egg and supports successful fertilization.