Miltefosine induces reproductive toxicity during sperm capacitation by altering PI3K/AKT signaling pathway

Eun Ju Jung, Woo Jin Lee, Jeong Won Bae, Woo Sung Kwon

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 80 μM 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.

Original languageEnglish
Article number104565
JournalEnvironmental Toxicology and Pharmacology
Volume111
DOIs
StatePublished - Oct 2024

Keywords

  • Capacitation
  • Miltefosine
  • PI3K/AKT signaling pathway
  • Sperm

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