Paternal SIRT1 Inhibition During Capacitation Imprints Histone 4 Hyperacetylation in Mouse Zygotes and Blastocysts

Sirtuin 1 (SIRT1) is a NAD⁺-dependent deacetylase involved in chromatin remodelling. In this study, we evaluated whether sperm SIRT1 inhibition affects early embryonic chromatin dynamics. Sperm were treated with sirtinol during capacitation or during both capacitation and fertilization. SIRT1 inhibition increased acH4K16 in the male pronucleus without affecting SIRT1 levels, whereas the female pronucleus remained largely unchanged, except for reduced SIRT1 when inhibition was extended to fertilization. Notably, embryos derived from treated sperm maintained elevated acH4K16 at the blastocyst stage. These findings indicate that sperm SIRT1 modulation can influence paternal chromatin remodelling and early embryonic epigenetic regulation.