title: Effect of oxamic analogues on functional mice sperm parameters.
abstract: The present study evaluates the effect of oxamate derivatives (N-ethyl, N-propyl, N-butyl oxamates) on functional murine sperm parameters, towards a new male non-hormonal contraceptive. These derivatives are selective inhibitors of lactate dehydrogenase-C4 (LDH-C4). LDH-C4 is a sperm-specific enzyme that plays an important role in ATP production for maintaining progressive motility as well as to induce capacitation and hyperactivation. The results demonstrate that all oxamate derivatives selectively inhibited LDH-C4 in mouse sperm extracts. The IC(50) values for hexokinase and glyceraldehyde-3-phosphate dehydrogenase were at least an order of magnitude greater than LDH-C4 IC(50) values. Prodrugs of oxamate derivatives assayed on sperm cells diminished normal sperm motility parameters, acrosome reaction, and cell viability in a concentration dependent manner. Also, we performed in vivo studies to determine the potential toxicity and possible contraceptive ability of these inhibitors. Mouse sperm were more sensitive to the N-butyl oxamate ethyl ester (NBOXet). Furthermore, results showed that NBOXet was of a low toxicity substance that diminished the total and progressive motility as well as the kinematic parameters of sperm cells. Data from in vitro and in vivo studies showed that N-butyl oxamate and its prodrug, are selective inhibitors of sperm LDH-C4, has low toxicity, and inhibits sperm progressive motility, offering some of the desirable characteristics of a male contraceptive: effect, low toxicity, and selectivity.
authors.affiliation: Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional , México.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Cordero-Martínez
authors.forename: Charmina
authors.initials: C
authors.lastname: Aguirre-Alvarado
authors.forename: Carlos
authors.initials: C
authors.lastname: Wong
authors.forename: Lorena
authors.initials: L
authors.lastname: Rodríguez-Páez
mesh_terms: D020101:Acrosome Reaction / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003276:Contraceptives, Oral / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010072:Oxamic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity; D013075:Sperm Capacitation / Q000187:drug effects; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D003276:Contraceptives, Oral; D000255:Adenosine Triphosphate; D010072:Oxamic Acid
keywords: Acrosome reaction; LDH-C4; inhibitor; oxamic acid; viability