CLASSIFICATION OF MALE FACTOR INFERTILITY RELEVANT TO IN-VITRO FERTILIZATION INSEMINATION STRATEGIES USING MANNOSE LIGANDS, ACROSOME STATUSAND ANTI-CYTOSKELETAL ANTIBODIES
S. Benoff et al., CLASSIFICATION OF MALE FACTOR INFERTILITY RELEVANT TO IN-VITRO FERTILIZATION INSEMINATION STRATEGIES USING MANNOSE LIGANDS, ACROSOME STATUSAND ANTI-CYTOSKELETAL ANTIBODIES, Human reproduction, 11(9), 1996, pp. 1905-1918
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.