Serotonergic signals enhanced hamster sperm hyperactivation

In the present study, we investigated the regulatory mechanisms underlying sperm hyperactivation enhanced by 5-hydroxytryptamine (5-HT) in hamsters. First, we examined the types of 5-HT receptors that regulate hyperactivation. Hyperactivation was significantly enhanced by 5-HT(2A) and 5-HT(4) receptor agonists. Moreover, the results of the motility assay revealed that 5-HT(2A), 5-HT(3), and 5-HT(4) receptor agonists significantly decreased the velocity and/or amplitude of sperm. Under 5-HT(2) receptor stimulation, hyperactivation was associated with phospholipase C (PLC), inositol 1,4,5-trisphosphate (IP(3)) receptor, soluble adenylate cyclase (sAC), and protein kinase A (PKA). In contrast, under 5-HT(4) receptor stimulation, hyperactivation was associated with transmembrane adenylate cyclase (tmAC), sAC, PKA, and CatSper channels. Accordingly, under the condition that sperm are hyperactivated, 5-HT likely stimulates PLC/IP(3) receptor signals via the 5-HT(2A) receptor and tmAC/PKA/CatSper channel signals via the 5-HT(4) receptor. After sAC and PKA are activated by these stimulations, sperm hyperactivation is enhanced.