Miltefosine Induces Reproductive Toxicity During Sperm Capacitation by Altering PI3K/AKT Signaling Pathway.
Environ Toxicol Pharmacol
; : 104565, 2024 Sep 10.
Article
en En
| MEDLINE
| ID: mdl-39265707
ABSTRACT
Miltefosine is the first and only drug approved for the treatment of leishmaniasis. It is also known as a PI3K/AKT signaling pathway inhibitor utilized in anti-cancer or anti-viral therapies. However, the impact of miltefosine on male fertility has not been fully understood. Therefore, this study was performed to investigate the effects of miltefosine on sperm function during capacitation. Duroc spermatozoa were exposed to 0, 2.5, 5, 10, 20, 40, and 80µM miltefosine and induced for capacitation. Our results showed that miltefosine dramatically increased the expression of PI3K/AKT signaling pathway-associated proteins. Sperm motility, motion kinetics, capacitation, and tyrosine phosphorylation were significantly suppressed by miltefosine. However, intracellular ATP levels and cell viability were not significantly affected. Our findings suggest that miltefosine may disrupt sperm function by abnormally increasing the levels of PI3K/AKT signaling pathway-associated proteins. Therefore, the harmful effects of miltefosine on male reproduction should be considered when using this drug.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Environ Toxicol Pharmacol
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Países Bajos