title: The opioid peptide beta-endorphin stimulates acrosome reaction in human spermatozoa.
abstract: The acrosome reaction occurs in vivo following sperm capacitation and is essential for the acquisition of sperm fertilization ability. However, little is known about the molecular identity of the physiological acrosome reaction regulators. In addition to progesterone, which is produced by cumulus oophorus cells and known to regulate acrosome reaction by activating the specific calcium channel CatSper, endogenous opioid peptides such as beta-endorphin and met-enkephalin are present at high concentrations in the follicular fluid suggesting that the opioid system may be involved in the mechanisms regulating the acrosome reaction in humans. By using Reverse Transcription-PCR, western blot and immunofluorescence approaches, we described the presence and localization of the beta-endorphin precursor, pro-opiomelanocortinin the middle section and in flagellum of human spermatozoa, and inside the seminiferous tubules of human testis. Flow cytometry and intracellular calcium analyses showed that beta-endorphin causes an inversely dose-dependent increase in the percentage of acrosome-reacted sperm cells by a calcium-independent protein kinase C pathway. These findings are important for future studies of sperm physiology and provide new insight into the function of the opioid system as a target of fertility management.
authors.affiliation: Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Urizar-Arenaza
authors.affiliation: Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.
authors.forename: H
authors.initials: H
authors.lastname: Estomba
authors.affiliation: Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Muñoa-Hoyos
authors.affiliation: Human Reproduction Unit, Cruces Hospital, BioCruces, University of the Basque Country, Basque Country, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Matorras
authors.affiliation: Human Reproduction Unit, Cruces Hospital, BioCruces, University of the Basque Country, Basque Country, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Esposito
authors.affiliation: Biological Chemistry Chemical Research Institute - CSIC/University of Seville, Seville, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Candenas
authors.affiliation: Biological Chemistry Chemical Research Institute - CSIC/University of Seville, Seville, Spain.
authors.forename: F M
authors.initials: FM
authors.lastname: Pinto
authors.affiliation: Department of Cellular Biology and Histology, Faculty of Pharmacy, University of the Basque Country(UPN/EHU), Vitoria-Gasteiz, Alava, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Valdivia
authors.affiliation: Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Irazusta
authors.affiliation: Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Subirán
mesh_terms: D020101:Acrosome Reaction / Q000502:physiology*; D006801:Humans; D008297:Male; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012671:Seminiferous Tubules / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D013075:Sperm Capacitation / Q000502:physiology*; D013094:Spermatozoa / Q000378:metabolism / Q000502:physiology*; D001615:beta-Endorphin / Q000378:metabolism*
chemical_list: D011374:Progesterone; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; C115197:calcium-independent protein kinase C; D011493:Protein Kinase C
keywords: acrosome reaction; male fertility; opioid peptides; signalling pathways; spermatozoa