Binding of arylsulfatase A to mouse sperm inhibits gamete interaction and induces the acrosome reaction.
We have shown previously that male germ cell-specific sulfoglycolipid, sulfogalactosylglycerolipid (SGG), is involved in sperm-zona pellucida binding, and that SGG and its desulfating enzyme, arylsulfatase A (AS-A), coexist in the same sperm head area. However, AS-A exists at a markedly low level in sperm as compared to SGG (i.e., 1/400 of SGG molar concentration). In the present study, we investigated whether perturbation of this molar ratio would interfere with sperm-egg interaction. We demonstrated that purified AS-A bound to the mouse sperm surface through its high affinity with SGG. When capacitated, Percoll gradient-centrifuged mouse sperm were treated for 1 h with various concentrations of AS-A, their binding to zona-intact eggs was inhibited in a dose-dependent manner and reached the background level with 63 nM AS-A. This inhibition could be partially explained by an increase in premature acrosome reaction. The acrosome-reacted sperm population of the 63 nM AS-A-treated sperm sample was twice that of the control sample (treated with 63 nM ovalbumin) at 1 h (i.e., 32% vs. 15%) and rose to 53% at 2 h. This induction was presumably due to SGG aggregation attributed to AS-A, existing as a dimer at neutral pH, and could be mimicked by anti-SGG immunoglobulin (Ig) G/IgM + secondary IgG antibody. Drastic inhibition (75%) of in vivo fertilization was also observed in females inseminated with sperm suspension containing 630 nM AS-A as compared to the rate in females inseminated with sperm suspension included with 630 nM ovalbumin. Our results demonstrate a promising potential for AS-A as a nonhormonal, vaginal contraceptive.
Carmona
Euridice
E
Hormones/Growth/Development Group, Ottawa Health Research Institute, Ottawa, Ontario, Canada K1Y 4E9.
Weerachatyanukul
Wattana
W
Xu
Hongbin
H
Fluharty
Arvan
A
Anupriwan
Araya
A
Shoushtarian
Ali
A
Chakrabandhu
Krittalak
K
Tanphaichitr
Nongnuj
N
D020101:Acrosome Reaction / Q000187:drug effects*; D000818:Animals; D002553:Cerebroside-Sulfatase / Q000008:administration & dosage* / Q000378:metabolism*; D003271:Contraceptive Agents, Female; D019281:Dimerization; D038983:Galactolipids / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000494:pharmacology; D007075:Immunoglobulin M / Q000494:pharmacology; D007315:Insemination, Artificial; D008099:Liver / Q000737:chemistry; D008297:Male; D051379:Mice; D013075:Sperm Capacitation; D013084:Sperm-Ovum Interactions / Q000187:drug effects*; D013094:Spermatozoa / Q000378:metabolism*; D015044:Zona Pellucida / Q000378:metabolism
D003271:Contraceptive Agents, Female; D038983:Galactolipids; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C414346:sulfogalactosylglycerolipid; D002553:Cerebroside-Sulfatase