Figure 1.

The production of gut microbiota-derived 5-HT and utilization in spermatozoa. (1) Gut microbiota improve tryptamine by expressing tryptophan decarboxylase (TPD), and secrete SCFAs to promote 5-HT by stimulating ECs expressing tryptophan hydroxylase (TPH1), selective reuptake transporter (SERT) and Indoleamine2,3-dioxygenase1 (IDO1). After serum 5-HT passes testis through blood circulation and enters sperm membrane through SERT, it activates tmAC and opens CatSper, resulting in Ca2+ influx increasingly, activating PKA, ultimately enhancing sperm hyperactivation and promoting sperm motility. (2) 5-HT in green suggests that recent research has only shown elevated levels in the central nervous system. It remains to be confirmed whether the gut microbiota can raise the levels of 5-HT in the testes.