TY - JOUR
T1 - Miltefosine induces reproductive toxicity during sperm capacitation by altering PI3K/AKT signaling pathway
AU - Jung, Eun Ju
AU - Lee, Woo Jin
AU - Bae, Jeong Won
AU - Kwon, Woo Sung
N1 - Publisher Copyright:
© 2024 Elsevier B.V.
PY - 2024/10
Y1 - 2024/10
N2 - 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.
AB - 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.
KW - Capacitation
KW - Miltefosine
KW - PI3K/AKT signaling pathway
KW - Sperm
UR - http://www.scopus.com/inward/record.url?scp=85203425174&partnerID=8YFLogxK
U2 - 10.1016/j.etap.2024.104565
DO - 10.1016/j.etap.2024.104565
M3 - Article
C2 - 39265707
AN - SCOPUS:85203425174
SN - 1382-6689
VL - 111
JO - Environmental Toxicology and Pharmacology
JF - Environmental Toxicology and Pharmacology
M1 - 104565
ER -