Tryptophan promotes sperm hyperactivation in hamsters via 5-hydroxytryptamine biosynthesis within sperm

L-tryptophan (Trp), an essential amino acid, is a precursor of 5-hydroxytryptamine (5-HT; also known as serotonin) that promotes mammalian sperm hyperactivation. Since mammalian sperm contain Trp hydroxylase (TPH), they may contribute to 5‑HT biosynthesis. Therefore, this study aimed to examine the effect of Trp on hamster sperm hyperactivation and determine whether sperm are involved in 5-HT biosynthesis. Trp significantly enhanced sperm hyperactivation via the 5-HT₄ receptor and its associated signals. In contrast, D-tryptophan did not affect sperm hyperactivation. Furthermore, hamster sperm contained the 5-HT biosynthesis enzymes TPH and aromatic L-amino acid decarboxylase (AADC). Additionally, hamster sperm secreted 5-HT. Trp-enhanced hyperactivation and 5-HT secretion were significantly inhibited by TPH and AADC inhibitors. Overall, our findings suggest that Trp enhanced sperm hyperactivation through the biosynthesis of 5-HT within the sperm.