Effect of oxamic analogues on functional mice sperm parameters. (August 2014)

• Record Type: Journal Article
• Authors: Cordero-Martínez, Joaquín; Aguirre-Alvarado, Charmina; Wong, Carlos; Rodríguez-Páez, Lorena
• Is Part Of: Systems biology in reproductive medicine. Volume 60:Number 4(2014:Aug.)
• Page Start: 189
• Page End: 198
• Publication Date: 2014-08
• Subjects: Systems biology -- Periodicals; Andrology -- Periodicals; Generative organs, Male -- Diseases -- Periodicals; Biological systems -- Periodicals; Reproductive health -- Periodicals; Human reproduction -- Periodicals; 612.61
• DOI: 10.3109/19396368.2014.902144
• Languages: English
• ISSNs: 1939-6368

Abstract

<abstract> <title>Abstract</title> <p>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<sub>50</sub> values for hexokinase and glyceraldehyde-3-phosphate dehydrogenase were at least an order of magnitude greater than LDH-C4 IC<sub>50</sub> 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 <italic>in vivo</italic> 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 i<italic>n vitro</italic> and <italic>in vivo</italic> 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.</p> </abstract>