米替福辛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 PI3K/AKT 信号通路抑制剂，用于抗癌或抗病毒治疗。然而，米替福辛对男性生育能力的影响尚未完全了解。因此，本研究旨在探讨米替福辛对获能过程中精子功能的影响。将杜洛克精子暴露于 0、2.5、5、10、20、40 和 80μM 米替福辛并诱导获能。我们的结果表明，米替福辛显着增加 PI3K/AKT 信号通路相关蛋白的表达。米替福辛显着抑制精子活力、运动动力学、获能和酪氨酸磷酸化。然而，细胞内 ATP 水平和细胞活力并未受到显着影响。我们的研究结果表明，米替福辛可能通过异常增加 PI3K/AKT 信号通路相关蛋白的水平来破坏精子功能。因此，使用该药时应考虑米替福辛对男性生殖的有害影响。版权所有 © 2024 Elsevier B.V. 保留所有权利。

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.Copyright © 2024 Elsevier B.V. All rights reserved.