The GPI‐anchored CD52 antigen of the sperm surface interacts with semenogelin and participates in clot formation and liquefaction of human semen

Abstract

CD52 is a human glycosylphosphatidylinositol (GPI)-anchored antigen exclusively expressed in leukocytes and epididymal cells. It is also present in sperm, being inserted in their plasma membrane as they pass through the epididymis. In a previous paper we identified a new CD52 form without GPI anchor by fast performance liquid chromatography (FPLC) fractionation of semen components. The form has a lower negative charge than the GPI-anchored form and occurs as the only CD52 form in prostasome-free seminal plasma. It was also found associated with the ejaculated sperm, but in contrast to the GPI-anchored one, it is lost during the capacitation process. In this paper we indicate that (1) the GPI-anchored CD52 of the sperm surface serves as receptor for semenogelin I during clot formation, (2) liquefaction involves cleavage of the GPI anchor from certain CD52 molecules, releasing sperm from the clot and the soluble antigen bound to semenogelin fragments into the seminal plasma and (3) the clot is a sponge-like structure housing sperm. Soluble CD52 was immunopurified from the soluble CD52-containing FPLC fraction using CAMPATH-1G and was found to be complexed with a semenogelin-derived peptide of the carboxyl terminal portion of semenogelin I, having the sequence SQTEKLVAGKQI and starting from amino acid 376. Immunoprecipitation and immunoblot analyses using CAMPATH-1G and anti-semenogelin as immunoprecipitating antibodies and anti-gp20 and anti-semenogelin as immunoblot detectors of the corresponding antigens, confirmed that the soluble CD52 formed a complex with semenogelin. The semenogelin-CD52 soluble form was found to be a direct consequence of the liquefaction process since only the GPI-anchored CD52 was recovered in uniquefied semen after recovering sperm and seminal plasma by urea solubilization of the clot.

Association of Seminal Plasma Motility Inhibitors/Semenogelins with Sperm in Asthenozoospermia-Infertile Men

“…This finding supports the hypothesis that asthenozoospermia is not caused by the presence of soluble Sgs in seminal plasma but by the presence of these Sgs in association with the spermatozoa. However, the molecular mechanism underlying the binding of SPMI to sperm is still unclear, and there are some factors that mediate SPMI binding to the sperm membrane, i.e., serine peptidase inhibitor-like molecules with Kunitz and WAP domains 1 (SPINLW1; eppin) [22] and CD52 (glycosylphosphatidylinositol; GPI-anchored antigen) [23] in humans. Moreover, SVS2, a protein that is homologous to Sgs in mice, selectively interacts with ganglioside GM1 on the sperm membrane to inhibit capacitation [24] .…”

Surface protein profiling of prostate-derived extracellular vesicles by mass spectrometry and proximity assays

“…Yang and colleagues have already demonstrated that these proteins are integral constituents of SF-EVs 25 . SEMG 1 has been found in complex with both the glycosylphosphatidylinositol (GPI)-anchored and soluble CD52, and it has been hypothesized that GPI-anchored CD52 serves as a dock for SEMG1 in anchoring the sperm cells to form clots 65 , later degraded by PSA to enable sperm motility. Recent studies found a negative correlation between sperm motility and the proportion of SEMGs bound spermatozoa 66,67 .…”

Production and characterization of a human antisperm monoclonal antibody against CD52g for topical contraception in women

“…Another potential limitation of this research is that HCA could interfere with normal functions of CD52g, which are largely unknown. A report from Flori et al [60] provided evidence that CD52g anchors sperm to semenogelin in the semen clot that forms minutes after intercourse; it is unknown whether HCA affects this process. A final limitation is that the study was conducted in vitro, and a clinical trial will be required to determine the in vivo contraceptive efficacy of HCA.…”