title: Glycodelin-S in human seminal plasma reduces cholesterol efflux and inhibits capacitation of spermatozoa.
abstract: Tight control of sperm capacitation is important for successful fertilization. Glycodelin-S is one of the most abundant glycoproteins in the human seminal plasma. However, its function is unclear. We investigated the role of glycodelin-S on capacitation of human spermatozoa. Binding kinetics experiments demonstrated the presence of two saturable and reversible binding sites of glycodelin-S on human spermatozoa. Differently glycosylated other isoforms of glycodelin, glycodelin-A and -F, did not compete with glycodelin-S for these binding sites, suggesting that the glycodelin-S binding sites are different from those of the other isoforms. Indirect immunofluorescent staining revealed specific binding of glycodelin-S around the sperm head. This immunoreactivity was greatly reduced in spermatozoa that had migrated through the cervical mucus surrogates. Glycodelin-S at physiological concentrations significantly reduced the bovine serum albumin and cyclodextrin-induced cholesterol efflux and down-regulated the adenylyl cyclase/protein kinase A/tyrosine kinase signaling pathway, resulting in suppression of capacitation. Deglycosylation abolished glycodelin-S binding and the effect of glycodelin-S on bovine serum albumin-induced capacitation. This indicates that the carbohydrate moiety of glycodelin-S is critical for the function of the molecule. It is concluded that glycodelin-S in seminal plasma maintains the uncapacitated state of human spermatozoa.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China.
authors.forename: Philip C N
authors.initials: PC
authors.lastname: Chiu
authors.forename: Man-Kin
authors.initials: MK
authors.lastname: Chung
authors.forename: Heng-Yan
authors.initials: HY
authors.lastname: Tsang
authors.forename: Riitta
authors.initials: R
authors.lastname: Koistinen
authors.forename: Hannu
authors.initials: H
authors.lastname: Koistinen
authors.forename: Markku
authors.initials: M
authors.lastname: Seppala
authors.forename: Kai-Fai
authors.initials: KF
authors.lastname: Lee
authors.forename: William S B
authors.initials: WS
authors.lastname: Yeung
mesh_terms: D000177:Acrosome / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism*; D000071816:Glycodelin; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D011257:Pregnancy Proteins / Q000378:metabolism*; D011485:Protein Binding; D012661:Semen / Q000166:cytology / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013075:Sperm Capacitation / Q000502:physiology*; D013094:Spermatozoa / Q000502:physiology*
chemical_list: D000071816:Glycodelin; D006023:Glycoproteins; D007457:Iodine Radioisotopes; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D012710:Serum Albumin, Bovine; D002784:Cholesterol