Sperm Epidermal Growth Factor Receptor (EGFR) Mediates alpha 7 Acetylcholine Receptor (AChR) Activation to Promote Fertilization

To attain fertilization the spermatozoon binds to the egg zona pellucida (ZP) via sperm receptor(s) and undergoes an acrosome reaction (AR). Several sperm receptors have been described in the literature; however, the identity of this receptor is not yet certain. In this study, we suggest that the alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) might be a sperm receptor activated by ZP to induce epidermal growth factor receptor (EGFR)-mediated AR. We found that isolated ZP or alpha 7 agonists induced the AR in sperm from WT but not alpha 7-null spermatozoa, and the induced AR was inhibited by alpha 7 or EGFR antagonists. Moreover, alpha 7-null sperm showed very little binding to the egg, and microfluidic affinity in vitro assay clearly showed that alpha 7nAChR, as well as EGFR, interacted with ZP3. Induction of EGFR activation and the AR by an alpha 7 agonist was inhibited by a Src family kinase (SFK) inhibitor. In conclusion we suggest that activation of alpha 7 by ZP leads to SFK-dependent EGFR activation, Ca2+ influx, and the acrosome reaction.