The effects of serotonin (5-hydroxytryptamine) on histone acetylation in early porcine embryos

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter with emerging roles in mammalian embryonic development. However, its epigenetic effects on early porcine embryos remain poorly understood. This study investigated the impact of 5-HT on histone acetylation and its regulatory mechanisms during early porcine embryo development. Using parthenogenetic embryos, we treated blastocyst, 4-cell, and 2-cell stage embryos with 5-HT and analyzed histone acetylation levels (H3K9Ac and H4K16Ac) and the expression of histone-modifying enzymes (HDAC1, HDAC2, HDAC3, and KAT8). Our results revealed that 5-HT significantly increased histone acetylation at the 4-cell stage but decreased it at the blastocyst stage. These changes were associated with altered expression of histone deacetylases (HDAC2 and HDAC3) and acetyltransferase (KAT8). Specifically, 5-HT upregulated KAT8 and downregulated HDAC2 and HDAC3 at the 4-cell stage, leading to elevated histone acetylation. Conversely, at the blastocyst stage, 5-HT increased HDAC1 and HDAC3 expression while reducing KAT8 activity, resulting in decreased histone acetylation. These findings demonstrate that 5-HT modulates histone acetylation by regulating the balance between histone acetyltransferases and deacetylases, thereby influencing gene expression and embryonic development in pigs. This study provides new insights into the epigenetic role of 5-HT in early embryogenesis and its potential applications in reproductive technologies.