Methods: In this study they performed N-terminal sequence analysis of gp20, a 20 kDa sialoglycoprotein on the human sperm surface previously identified by radiolabelling of the sialic acid residues of sperm surface.
Findings: They found 100% identity with the N-terminus of CD52, an antigen expressed on almost all human leukocytes. They show that, like CD52, gp20 behaves as a glycosylphosphatidylinositol (GPI)-anchored protein and that anti-gp20 antiserum reacts with an antigen on leukocytes of the same molecular weight as CD52. Using CAMPATH-1 or alemtuzumab, the monoclonal antibody against CD52, in fluorescent staining of capacitated spermatozoa, Western blot analysis and the zona-free hamster egg penetration test, they found that the effect of this antibody was different from that of our anti-gp20. Western blot analysis revealed a well-defined 20 kDa band with anti-gp20, whereas a 14-20 kDa band was detected with CAMPATH-1. Anti-gp20 stained the equatorial region of the sperm head, whereas CAMPATH-1 stained the tail in immunofluorescence analysis of capacitated spermatozoa. A dose-dependent inhibitory effect was seen with CAMPATH-1, similar to that previously detected with anti-gp20, in a zona-free hamster egg penetration test. However, with CAMPATH-1 agglutination of motile spermatozoa was detected, and this was not present with anti-gp20.
Conclusions: This suggests that the epitopes recognized by the two antibodies are different.
The sperm glycocalyx represents the primary interface between the male gamete and its environment, and gamete interaction inevitably involves interaction with this structure. Thus, it has potential significance as a target for antibodies that inhibit sperm function. Still, little is known about the components and biological role of the sperm glycocalyx. Despite the apparent complexity of the sperm membrane, surface carbohydrate labelling experiments show a high selectivity suggesting that carbohydrate side chains of CD52, an unusually short, bipolar glycopeptide of epididymal origin, form major components of the sperm glycocalyx in all mammalian species investigated. Acquisition of the highly sialylated, lipid-anchored CD52 antigen is one of the few well-defined modifications that occur to the sperm membrane during epididymal passage. It would explain changes in lectin-binding patterns and also the remarkable surface charge differences occurring during epididymal transit, most probably attributable to its terminal sialic acid residues. CD52 seems to be immunodominant on human spermatozoa, and antibodies directed against it can agglutinate and completely immobilize human sperm in the presence of complement. Expression of the same peptide backbone in lymphocytes had largely discounted its consideration as a candidate for contraceptive development. However, the recent proof of male-specific modifications indicates the feasibility of this approach.
Kyriacou et al. Germ cell damage and Leydig cell insufficiency in recipients of nonmyeloablative transplantation for haematological malignancies..Bone Marrow Transplant. 2003 Jan;31(1):45-50.
Background: Most bone marrow transplant recipients are infertile due to reversible or irreversible testicular failure. However, little is known about the gonadotoxic potential of the newly introduced nonmyeloablative transplants.
Objective: They undertook a 24-month longitudinal study in a cohort of 32 recipients of nonmyeloablative transplantation to test whether the combined regimen of fludarabine, melphalan and CAMPATH-1H can induce damage to germ cell (GC) and Leydig cell (LC) compartments.
Methods: Testicular function was assessed immediately prior to transplantation and at four time points post-transplant to compare hormonal levels before and after the procedure. Two other groups treated with BEAM- and TBI-related regimes were also included in the study group for comparative purposes. GC function was assessed by measuring basal serum follicle stimulating hormone (FSH). LC function was assessed by measuring basal luteinising hormone (LH) and testosterone (T) levels. LC reserve was assessed by measuring the T/LH ratio.
Results: As a group, patients who received a non myeloablative transplant sustained severe damage to the GC compartment, as evident from a substantial elevation in the FSH level post-transplant (12 IU/l vs 18.4 IU/l, P<0.001). Similar to the GC injury, patients as a group sustained significant damage to the LC compartment following the transplant (5.4 IU/l vs 9.6 IU/l, P<0.001). In general, patients had reduced LC reserve post-BMT, as evident from a diminished T/LH ratio (2.6 pretransplant vs 1.6 post-transplant P=0.05). Patients who received a nonmyeloablative transplant had a similar effect on the GC and LC compartments compared to those who had a BEAM autograft. On the other hand, patients who received a TBI-based transplant sustained more damage to their GC and LC compartments compared to those who received a nonmyeloblative transplant; however, this was not statistically significant (P=0.09).
Conclusions: Our data suggest that this type of regimen is potentially gonadotoxic and consideration should be given to fertility counselling and testosterone replacement therapy post-transplant.
CoI: multiple