Regulation of spermatozoal capacitation by serotonin

Mammalian spermatozoa begin swimming after ejaculation. After spermatozoa enter the oviduct, they undergo capacitation, penetrate the oocyte envelope, and fertilize the oocytes. These processes occur spontaneously but are influenced by hormones and neurotransmitters. Serotonin [5-hydroxytryptamine (5-HT)] is a well-known neurotransmitter found in reproductive organs. In the female reproductive system, serotonin is synthesized in the cumulus cells and affects steroidogenesis, oocyte maturation, fertilization, and embryo development. Recent studies have suggested that serotonin is also synthesized in spermatozoa and can affect motility, hyperactivation, acrosome reaction, and the success of in vitro fertilization (IVF) in hamsters, humans, mice, and rats. Importantly, the effects of serotonin on sperm function are dose-dependent, at least in hamsters, and serotonin concentrations in the female reproductive tract fluctuate during ovulation. The effects of serotonin on sperm function are mediated by 5-HT receptors (mainly 5-HT₂ and 5-HT₄), which stimulate Ca²⁺ and cyclic AMP signaling, respectively. The 5-HT₂ receptor is involved in regulating motility and hyperactivation in hamsters, humans, and mice, whereas the 5-HT₄ receptor is involved in regulating hyperactivation, the acrosome reaction, and IVF success in hamsters, mice, and rats. Because the 5-HT₄ receptor is a common receptor in rodents associated with capacitation and IVF success and is stimulated by serotonin synthesized in spermatozoa, current evidence indicates that the 5-HT₄ receptor is especially important for the regulation of rodent spermatozoal functions regulated by serotonin.