CLASSIFICATION OF MALE FACTOR INFERTILITY RELEVANT TO IN-VITRO FERTILIZATION INSEMINATION STRATEGIES USING MANNOSE LIGANDS, ACROSOME STATUSAND ANTI-CYTOSKELETAL ANTIBODIES

Polyvalent mannose ligands in the presence of free mannose act as zona pellucida agonists which rapidly induce acrosome exocytosis in compet ent motile human sperm from fertile donors following in-vitro capacita tion, Quantification of the binding patterns of fluorescein isothiocya nate-labelled mannosylated albumins and of specific antisera which rec ognize mannose receptors and other related integral sperm membrane pro teins as well as the incidence of induced acrosome exocytosis after ca pacitation has allowed us to identify three categories of male inferti lity. Category 1 males have normozoospermic semen parameters, their sp ermatozoa have elevated sperm cholesterol values and fail to fertilize oocytes in vitro after standard short-term incubations, These spermat ozoa do not bind mannose ligands and do not show spontaneous or induce d acrosome reactions, but treatments to remove cholesterol from the sp ermatozoa (e.g. prolonged incubation in the presence of sterol accepte rs) confer the ability to fertilize, Cholesterol loading and unloading experiments have demonstrated the reversible character of sperm membr ane properties in category 1 male infertility, Category 2 males have n ormal-appearing spermatozoa in semen which express mannose ligand rece ptors on incubation, but fail to undergo acrosome reactions in respons e to mannose treatment, Interestingly, all category 2 males identified in this study have clinical varicocele, Category 3 males have semen w hich may be normozoospermic or teratozoospermic with, in some cases, h igh percentages of tapering spermatozoa in the absence of clinical var icocele, Spermatozoa from category 3 men are deficient in a superfamil y of integral membrane proteins whose cytoplasmic tails have myosin mo tors as identified by amino acid sequence analysis and anti-myosin ant ibody reactivity. Their spermatozoa do not express mannose ligand rece ptors or undergo induced acrosome reactions, Fertilization with catego ry 2 and 3 semen is only achieved by micromanipulation procedures, The se findings illustrate the practical application of basic research for infertility classification.