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Updated: Aug 18, 2026
High-Resolution Respirometry to Assess Mitochondrial Function in Human Spermatozoa
Published on: June 23, 2023
[Mitochondrial damage in human sperm caused by the antineoplastic agent betulinic acid]
S Dathe1, U Paasch, S Grunewald
1Klinik für Dermatologie, Venerologie und Allergologie des Universitätsklinikums Leipzig.
Background And Objective:
Human spermatozoa post-ejaculation show all elements of intrinsic (via mitochondria) and extrinsic (via death receptors) programmed cell death or apoptosis. One experimental therapeutic agent for malignant melanoma is betulinic acid (BA), a cytotoxic agent which induces intrinsic apoptosis via direct effects on mitochondria. To assess the potential side effects of systemic BA, its effects on motility, mitochondrial transmembrane potential (mTMP) and the apoptotic enzymes caspase-9 and -3, were monitored in human ejaculated spermatozoa.
Patients And Methods:
Semen samples from 33 healthy volunteers were examined after incubation with 60 microg/mL betulinic acid for 5 and 60 minutes.
Results:
Treatment with betulinic acid caused an immediate disruption of mitochondrial transmembrane potential and activation of the "death enzymes" caspase-9 and -3. The loss of mitochondrial potential was accompanied by a significant decrease of spermatozoal motility.
Conclusion:
Our results suggest that inducers of the mitochondrial pathway of apoptosis used in the treatment of malignant melanoma damage the sensitive mitochondria of spermatozoa.
Insights
Betulinic acid, used for melanoma treatment, disrupts sperm mitochondria and motility by activating apoptosis pathways. This suggests potential side effects on male fertility from this cancer therapy.
Area of Science:
- Reproductive Biology
- Cancer Therapeutics
- Cellular Biology
Background:
- Human spermatozoa undergo apoptosis, a programmed cell death process, involving both intrinsic (mitochondrial) and extrinsic (death receptor) pathways.
- Betulinic acid (BA) is an experimental agent for malignant melanoma that induces intrinsic apoptosis by directly affecting mitochondria.
Purpose of the Study:
- To investigate the potential side effects of systemic betulinic acid (BA) on human spermatozoa.
- To assess the impact of BA on sperm motility, mitochondrial transmembrane potential (mTMP), and key apoptotic enzymes (caspase-9 and -3).
Main Methods:
- Semen samples from 33 healthy volunteers were analyzed.
- Samples were incubated with 60 microg/mL of betulinic acid for 5 and 60 minutes.
Main Results:
- Betulinic acid rapidly disrupted the mitochondrial transmembrane potential (mTMP) in spermatozoa.
- This disruption led to the activation of caspase-9 and caspase-3, key enzymes in apoptosis.
- A significant decrease in sperm motility was observed concurrently with the loss of mTMP.
Conclusions:
- The study suggests that betulinic acid, an inducer of the mitochondrial apoptosis pathway, damages sperm mitochondria.
- These findings highlight potential adverse effects of BA, a melanoma therapeutic, on sperm quality and function.
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