TY - JOUR
T1 - Effect of oxamic analogues on functional mice sperm parameters
AU - Cordero-Martínez, Joaquín
AU - Aguirre-Alvarado, Charmina
AU - Wong, Carlos
AU - Rodríguez-Páez, Lorena
N1 - Funding Information:
This work was partially supported by research grants from the Secretaría de Investigación y Posgrado del Instituto Politécnico Nacional (SIP-IPN), México. CW and LRP are fellows of the COFAA-IPN and of the SNI-CONACyT. JCM and ChAA were fellows of the CONACyT and PIFI-IPN. The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported in the present manuscript.
PY - 2014/8
Y1 - 2014/8
N2 - 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 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.
AB - 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 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.
KW - Acrosome reaction
KW - Inhibitor
KW - LDH-C4
KW - Oxamic acid
KW - Viability
UR - http://www.scopus.com/inward/record.url?scp=84903304552&partnerID=8YFLogxK
U2 - 10.3109/19396368.2014.902144
DO - 10.3109/19396368.2014.902144
M3 - Artículo
C2 - 24654556
SN - 1939-6368
VL - 60
SP - 189
EP - 198
JO - Systems Biology in Reproductive Medicine
JF - Systems Biology in Reproductive Medicine
IS - 4
ER -