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

Area of Science:

• Reproductive biology
• Pharmacology
• Cell signaling

Background:

• Miltefosine is a key drug for leishmaniasis and investigated for anti-cancer/anti-viral uses.
• Its effects on male fertility remain largely uncharacterized.
• The PI3K/AKT signaling pathway is crucial for various cellular processes, including sperm function.

Purpose of the Study:

• To investigate the impact of miltefosine on sperm function during capacitation.
• To elucidate the role of the PI3K/AKT signaling pathway in miltefosine-induced effects on spermatozoa.

Main Methods:

• Duroc spermatozoa were treated with varying concentrations of miltefosine (0-80 μM).
• Sperm capacitation was induced following miltefosine exposure.
• Key parameters assessed included sperm motility, kinetics, capacitation, tyrosine phosphorylation, intracellular ATP, and cell viability.

Main Results:

• Miltefosine significantly increased the expression of PI3K/AKT pathway-associated proteins.
• Sperm motility, motion kinetics, capacitation, and tyrosine phosphorylation were markedly suppressed.
• Intracellular ATP levels and sperm viability remained unaffected by miltefosine treatment.

Conclusions:

• Miltefosine disrupts normal sperm function, potentially by aberrant activation of the PI3K/AKT signaling pathway.
• The findings highlight potential adverse effects of miltefosine on male reproductive health.
• Consideration of miltefosine's impact on male fertility is warranted during its clinical application.