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Home / Equine Research Bank / FASEB Bioadv / The effects of oxidative stress and intracellular calcium on...
FASEB bioAdvances2024; 6(6); 143-158; doi: 10.1096/fba.2023-00051

The effects of oxidative stress and intracellular calcium on mitochondrial permeability transition pore formation in equine spermatozoa.

Abstract: The in vitro storage of stallion spermatozoa for use in artificial insemination leads to oxidative stress and imbalances in calcium homeostasis that trigger the formation of the mitochondrial permeability transition pore (mPTP), resulting in premature cell death. However, little is understood about the dynamics and the role of mPTP formation in mammalian spermatozoa. Here, we identify an important role for mPTP in stallion sperm Ca2+ homeostasis. We show that stallion spermatozoa do not exhibit "classical" features of mPTP; specifically, they are resistant to cyclosporin A-mediated inhibition of mPTP formation, and they do not require exogenous Ca2+ to form the mPTP. However, chelation of endogenous Ca2+ prevented mPTP formation, indicating a role for intracellular Ca2+ in this process. Furthermore, our findings suggest that this cell type can mobilize intracellular Ca2+ stores to form the mPTP in response to low Ca2+ environments and that under oxidative stress conditions, mPTP formation preceded a measurable increase in intracellular Ca2+, and vice versa. Contrary to previous work that identified mitochondrial membrane potential (MMP) as a proxy for mPTP formation, here we show that a loss of MMP can occur independently of mPTP formation, and thus MMP is not an appropriate proxy for the detection of mPTP formation. In conclusion, the mPTP plays a crucial role in maintaining Ca2+ and reactive oxygen species homeostasis in stallion spermatozoa, serving as an important regulatory mechanism for normal sperm function, thereby contraindicating the in vitro pharmacological inhibition of mPTP formation to enhance sperm longevity.
© 2024 The Authors. FASEB BioAdvances published by Wiley Periodicals LLC on behalf of The Federation of American Societies for Experimental Biology.
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Publication Date: 2024-05-03 PubMed ID: 38846376PubMed Central: PMC11150759DOI: 10.1096/fba.2023-00051Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the relationship between oxidative stress, calcium balance and the formation of mitochondrial permeability transition pore (mPTP) in the sperm cells of horses. It shows that mPTP has a key role in managing calcium and reactive oxygen species in these sperm cells, which indicates that preventing mPTP formation to extend the lifespan of sperm cells could be counterproductive.

Key Findings

  • The study identified a significant role of mPTP in the calcium homeostasis (the balance within the cell) of horse sperm cells. The features of mPTP in these sperm cells did not match typical features seen in other cells.
  • The researchers demonstrated that these sperm cells didn’t need cyclosporin A, a common inhibitor for mPTP formation. Additionally, they didn’t require exogenous calcium (calcium from outside the cell) for mPTP formation.
  • However, by using a process called chelation to bind and remove endogenous calcium (calcium from inside the cell), they were able to prevent the formation of mPTP. This suggests that mPTP formation relies on calcium found within the cell.

Additional Insights

  • The study explained that mPTP formation could occur in response to low calcium environments, and oxidative stress situations could trigger this formation even before a measurable increase in intracellular calcium.
  • In contradiction to previous studies that suggested mitochondrial membrane potential (MMP) could be used as a measure of mPTP formation, the researchers found that a loss of MMP can occur on its own, without mPTP formation. Therefore, MMP is not a reliable indicator of mPTP.

Conclusion

  • The formation of the mitochondrial permeability transition pore (mPTP) is critical for sustaining the balance of calcium and reactive oxygen species in horse sperm cells. This study therefore suggests that inhibiting mPTP formation to improve the lifespan and function of sperm cells for artificial insemination might not be a beneficial strategy.

Cite This Article

APA
Gibb Z, Aitken RJ, Sheridan AR, Holt B, Waugh S, Swegen A. (2024). The effects of oxidative stress and intracellular calcium on mitochondrial permeability transition pore formation in equine spermatozoa. FASEB Bioadv, 6(6), 143-158. https://doi.org/10.1096/fba.2023-00051

Publication

FASEB bioAdvances
ISSN: 2573-9832
NlmUniqueID: 101733210
Country: United States
Language: English
Volume: 6
Issue: 6
Pages: 143-158

Researcher Affiliations

Gibb, Zamira
  • School of Environmental and Life Sciences, College of Engineering, Science and Environment The University of Newcastle Callaghan New South Wales Australia.
Aitken, Robert J
  • School of Environmental and Life Sciences, College of Engineering, Science and Environment The University of Newcastle Callaghan New South Wales Australia.
Sheridan, Alecia R
  • School of Environmental and Life Sciences, College of Engineering, Science and Environment The University of Newcastle Callaghan New South Wales Australia.
Holt, Brandan
  • Faculty of Health, School of Biomedical Sciences Queensland University of Technology Brisbane Queensland Australia.
Waugh, Stephanie
  • School of Environmental and Life Sciences, College of Engineering, Science and Environment The University of Newcastle Callaghan New South Wales Australia.
Swegen, Aleona
  • School of Environmental and Life Sciences, College of Engineering, Science and Environment The University of Newcastle Callaghan New South Wales Australia.

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