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.

中文翻译：

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Miltefosine 通过改变 PI3K/AKT 信号通路在精子获能过程中诱导生殖毒性


Miltefosine 是第一个也是唯一一个被批准用于治疗利什曼病的药物。它也被称为用于抗癌或抗病毒疗法的 PI3K/AKT 信号通路抑制剂。然而，miltefosine 对男性生育能力的影响尚不完全清楚。因此，本研究旨在探讨 miltefosine 对获能期间精子功能的影响。杜洛克精子暴露于 0 、 2.5 、 5 、 10 、 20 、 40 和 80 μM 米替福新并诱导获能。我们的结果表明，miltefosine 显着增加了 PI3K/AKT 信号通路相关蛋白的表达。miltefosine 显著抑制精子活力、运动动力学、获能和酪氨酸磷酸化。然而，细胞内 ATP 水平和细胞活力没有显着影响。我们的研究结果表明，miltefosine 可能通过异常增加 PI3K/AKT 信号通路相关蛋白的水平来破坏精子功能。因此，使用本药时应考虑米替福新对男性生殖的有害影响。