[Mitochondrial damage in human sperm caused by the antineoplastic agent betulinic acid].
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.


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.


CONCLUSIONS
Our results suggest that inducers of the mitochondrial pathway of apoptosis used in the treatment of malignant melanoma damage the sensitive mitochondria of spermatozoa.
Dathe
S
S
Klinik für Dermatologie, Venerologie und Allergologie des Universitätsklinikums Leipzig.
Paasch
U
U
Grunewald
S
S
Glander
H-J
HJ
D000970:Antineoplastic Agents / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000502:physiology*; D053978:Pentacyclic Triterpenes; D013094:Spermatozoa / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D014315:Triterpenes / Q000009:adverse effects*; D014463:Ultrasonography; D000094062:Betulinic Acid
D000970:Antineoplastic Agents; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D000094062:Betulinic Acid