Effect of oxamic analogues on functional mice sperm parameters.

Effect of oxamic analogues on functional mice sperm parameters. Syst Biol Reprod Med. 2014 Mar 21; Authors: Cordero-Martínez J, Aguirre-Alvarado C, Wong C, Rodríguez-Páez L Abstract 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 IC50 values for hexokinase and glyceraldehyde-3-phosphate dehydrogenase were at least an order of magnitude greater than LDH-C4 IC50 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 v...
Source: Systems Biology in Reproductive Medicine - Category: Reproduction Medicine Authors: Tags: Syst Biol Reprod Med Source Type: research