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期刊名称: Biology of Reproduction
Volume:87    Issue:5        Page:110-110

Sperm motility is lost in vitro as a consequence of mitochondrial free radical production and the generation of electrophilic aldehydes but can be significantly rescued by the presence of nucleophilic thiols期刊论文

作者: Aitken R. John Gibb Zamira Mitchell Lisa A Lambourne Sarah R Connaughton Haley S

页码: 110-110
被引频次: 83
期刊名称: Biology of Reproduction
ISSN: 0006-3363
卷期: Volume:87    Issue:5
语言: English
摘要: The prolonged incubation of human spermatozoa in vitro was found to induce a loss of motility associated with the activation of mitochondrial reactive oxygen species generation in the absence of any change in mitochondrial membrane potential. The increase in mitochondrial free radical production was paralleled by a loss of protein thiols and a concomitant rise in the formation of 4-hydroxynonenal, an electrophilic product of lipid peroxidation that was found to directly suppress sperm movement. These results prompted a search for nucleophiles that could counteract the action of such cytotoxic aldehydes, as a means of ensuring the long-term survival of spermatozoa in vitro. Four nucleophilic compounds were consequently assessed (penicillamine, homocysteine, N-acetylcysteine, and mercaptosuccinate) in three species (human, rat, and horse). The results of this analysis revealed drug and species specificity in the manner in which these compounds affected sperm function, with penicillamine conferring the most consistent, effective support. This prosurvival effect was achieved downstream of mitochondrial reactive oxygen species generation and was associated with the stabilization of 4-hydroxynonenal generation, the preservation of sperm thiols, and a reduction in 8-hydroxy-2'-deoxyguanosine formation. Theoretical calculations of Fe-S and Cu-S bond distances and corresponding binding energies suggested that the particular effectiveness of penicillamine may, in part, reflect the ability of this nucleophile to form stable complexes with transition metals that catalyze lipid peroxidation. The practical implications of these findings were indicated by the effective preservation of equine spermatozoa for 8 days at ambient temperature when the culture medium was supplemented with penicillamine.
相关主题: Gamete biology, Oxidative stress, Mitochondria, Sperm, Sperm motility and transport, sperm motility and transport, FERTILIZATION, LIPID-PEROXIDATION PRODUCTS, mitochondria, SEMINAL PLASMA, OXYGEN SPECIES GENERATION, DNA-DAMAGE, gamete biology, sperm, REPRODUCTIVE BIOLOGY, REDOX REGULATION, HUMAN-SPERMATOZOA, PEROXYNITRITE SCAVENGERS, CAPACITATION, oxidative stress, Reactive Oxygen Species - metabolism, Oxidative Stress, Sulfhydryl Compounds - pharmacology, Humans, Penicillamine - pharmacology, Rats, Male, Semen Preservation - veterinary, Mitochondria - metabolism, Aldehydes - metabolism, Sperm Motility - drug effects, Sulfhydryl Compounds - metabolism, Animals, Free Radicals - metabolism, Horses, Semen Preservation - methods, Spermatozoa - ultrastructure, Index Medicus,






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