Andrology: Classification of male factor infertility relevant to in-vitro fertilization insemination strategies using mannose ligands, acrosome status and anti-cytoskeletal antibodies

Abstract

Polyvalent mannose ligands in the presence of free mannose act as zona pellucida agonists which rapidly induce acrosome exocytosis in competent motile human sperm from fertile donors following in-vitro capacitation. Quantification of the binding patterns of fluorescein isothiocyanate-labelled mannosylated albumins and of specific antisera which recognize mannose receptors and other related integral sperm membrane proteins as well as the incidence of induced acrosome exocytosis after capacitation has allowed us to identify three categories of male infertility. Category 1 males have normozoospermic semen parameters, their spermatozoa have elevated sperm cholesterol values and fail to fertilize oocytes in vitro after standard short-term incubations. These spermatozoa do not bind mannose ligands and do not show spontaneous or induced acrosome reactions, but treatments to remove cholesterol from the spermatozoa (e.g. prolonged incubation in the presence of sterol acceptors) confer the ability to fertilize. Cholesterol loading and unloading experiments have demonstrated the reversible character of sperm membrane properties in category 1 male infertility. Category 2 males have normal-appearing spermatozoa in semen which express mannose ligand receptors on incubation, but fail to undergo acrosome reactions in response to mannose treatment. Interestingly, all category 2 males identified in this study have clinical varicocele. Category 3 males have semen which may be normozoospermic or teratozoospermic with, in some cases, high percentages of tapering spermatozoa in the absence of clinical varicocele. Spermatozoa from category 3 men are deficient in a superfamily of integral membrane proteins whose cytoplasmic tails have myosin motors as identified by amino acid sequence analysis and anti-myosin antibody reactivity. Their spermatozoa do not express mannose ligand receptors or undergo induced acrosome reactions. Fertilization with category 2 and 3 semen is only achieved by micromanipulation procedures. These findings illustrate the practical application of basic research for infertility classification.

Surface Expression of Complement Receptor gC1q-R/p33 Is Increased on the Plasma Membrane of Human Spermatozoa after Capacitation1

“…Inhibition of this enzyme activity results in a dose-dependent decrease in the number of sperm bound per egg [50][51][52]. Exogenous D-mannose inhibits sperm-zona interactions.…”

Identification and Characterization of a Novel Functional Estrogen Receptor on Human Sperm Membrane That Interferes with Progesterone Effects

“…Because levels of estradiol in the follicular fluid are similar to those inducing the observed nongenomic effects, the strict cross-talk between sperm membrane receptors for 17␤E 2 and P may be important for an appropriate timing of capacitation and AR in the female genital tract. Further studies are required to elucidate whether environmental chemicals with estrogen action might have similar effects on human sperm and to evaluate whether the absence of sperm response to P in several cases of idiopathic male infertility (27,59) may be attributable to alteration in the interactions between these two steroids.…”

Nongenomic Effects of Progesterone on Spermatozoa: Mechanisms of Signal Transduction and Clinical Implications

“…95% when the two tests are com bined. R ecently, others authors con rm ed these data [84][85][86] . The analysis of sperm responsiv eness to P is quite simple and highly speci c, does not require expensiv e equipment and, for the evaluation of is totally objectiv e and thus independent from the operator.…”