Activation of sperm EGFR by light irradiation is mediated by reactive oxygen species.
To acquire fertilization competence, spermatozoa must undergo several biochemical and motility changes in the female reproductive tract, collectively called capacitation. Actin polymerization and the development of hyperactivated motility (HAM) are part of the capacitation process. In a recent study, we showed that irradiation of human sperm with visible light stimulates HAM through a mechanism involving reactive-oxygen-species (ROS), Ca(2+) influx, protein kinases A (PKA), and sarcoma protein kinase (Src). Here, we showed that this effect of light on HAM is mediated by ROS-dependent activation of the epidermal growth factor receptor (EGFR). Interestingly, ROS-mediated HAM even when the EGFR was activated by EGF, the physiological ligand of EGFR. Light irradiation stimulated ROS-dependent actin polymerization, and this effect was abrogated by PBP10, a peptide which activates the actin-severing protein, gelsolin, and causes actin-depolymerization in human sperm. Light-stimulated tyrosine phosphorylation of Src-dependent gelsolin, resulting in enhanced HAM. Thus, light irradiation stimulates HAM through a mechanism involving Src-mediated actin polymerization. Light-stimulated HAM and in vitro-fertilization (IVF) rate in mouse sperm, and these effects were mediated by ROS and EGFR. In conclusion, we show here that irradiation of sperm with visible light, enhances their fertilization capacity via a mechanism requiring ROS, EGFR and HAM.
The Mina & Everard Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Shiran
S
Shahar
Pnina
P
Hillman
Rachel
R
Lubart
Debby
D
Ickowicz
Haim
H
Breitbart
D000199:Actins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro; D018260:Gelsolin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation / Q000528:radiation effects; D058105:Polymerization / Q000528:radiation effects; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013075:Sperm Capacitation / Q000528:radiation effects*; D013076:Sperm Count; D013081:Sperm Motility / Q000528:radiation effects; D013094:Spermatozoa / Q000378:metabolism / Q000528:radiation effects*
D000199:Actins; D018260:Gelsolin; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C527698:gelsolin (160-169); C512478:EGFR protein, human; D066246:ErbB Receptors; D016392:Proto-Oncogene Proteins pp60(c-src); D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium