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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.
Abstract: 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.
Publication Date: 2012-11-08 PubMed ID: 22933515DOI: 10.1095/biolreprod.112.102020Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article discusses how the motility of sperm in vitro (in an artificial environment) can be negatively affected by free radicals from mitochondrial activities. It also provides evidence that the presence of nucleophilic thiols can help to significantly preserve the sperm’s ability to move.
Increased Mitochondrial Free Radicals
- The study observed that extended incubation of human sperm in vitro led to reduced motility attributed to increased production of mitochondrial reactive oxygen species (ROS). Notably, there was no change in the mitochondrial membrane’s potential during this process.
- The increase in radical production was associated with a reduction in protein thiols. This outcome coincided with the increased formation of 4-hydroxynonenal, a by-product of lipid peroxidation known to hinder sperm movement.
Seeking Nucleophile Solutions
- The results prompted a search for nucleophiles – chemicals that could neutralize the aldehydes, which were harming the sperm, thereby ensuring their long-term survival in vitro.
- The study tested four nucleophilic compounds (penicillamine, homocysteine, N-acetylcysteine, and mercaptosuccinate) in human, rat, and horse sperm.
- The research found that the compounds had different effects on sperm function depending on the species and the specific drug used. The most consistent and effective solution was found to be penicillamine.
How Penicillamine Works
- Penicillamine’s protective effect functioned downstream of mitochondrial ROS generation. It was linked with the stabilization of 4-hydroxynonenal generation, the preservation of sperm thiols, and a reduction in 8-hydroxy-2′-deoxyguanosine formation.
- The researchers theorized that penicillamine’s effectiveness may in part be because it can form stable complexes with transition metals that catalyze lipid peroxidation.
Practical Implications
- The study’s practical implications were highlighted by the successful preservation of horse sperm for eight days at room temperature by adding penicillamine to the culture medium.
Cite This Article
APA
Aitken RJ, Gibb Z, Mitchell LA, Lambourne SR, Connaughton HS, De Iuliis GN.
(2012).
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.
Biol Reprod, 87(5), 110.
https://doi.org/10.1095/biolreprod.112.102020 Publication
Researcher Affiliations
- Priority Research Centre for Reproductive Science, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales, Australia. john.aitken@newcastle.edu.au
MeSH Terms
- Aldehydes / metabolism
- Animals
- Free Radicals / metabolism
- Horses
- Humans
- Male
- Mitochondria / metabolism
- Oxidative Stress
- Penicillamine / pharmacology
- Rats
- Reactive Oxygen Species / metabolism
- Semen Preservation / methods
- Semen Preservation / veterinary
- Sperm Motility / drug effects
- Spermatozoa / ultrastructure
- Sulfhydryl Compounds / metabolism
- Sulfhydryl Compounds / pharmacology
Citations
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