Palmitoylation of C4BPA in porcine epididymosomes mitigates complement C4-mediated damage to sperm

Previous studies have revealed the expression of anti-complement factors on the surface of sperm across various species to resist attacks from complement components in reproductive tracts. Here we show that the anti-complement factor The caput of the porcine epididymis specifically expresses C4BPA, which is then transported to the surface of sperm via epididymosomes. The presence of C4BPA in epididymosomes depends on its palmitoylation modification, specifically at the Cys13 and Cys23 residues. ZDHHC8 has been pinpointed as the palmitoyl transferase that carries out this modification. Palmitoylated C4BPA in epididymosomes significantly resists attacks by complement C4 on sperm, maintaining porcine sperm motility. Our findings reveal a critical role for palmitoylated C4BPA in mitigating C4-mediated damage to sperm, highlighting its physiological relevance in preserving sperm motility and viability.