Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Gyeongsangbuk-do 37224, Republic of Korea.
Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Gyeongsangbuk-do 37224, Republic of Korea; Research Institute for Innovative Animal Science, Kyungpook National University, Sangju, Gyeongsangbuk-do 37224, Republic of Korea.
Environ Toxicol Pharmacol. 2024 Oct;111:104565. doi: 10.1016/j.etap.2024.104565. Epub 2024 Sep 10.
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.
米替福新是第一种也是唯一一种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治疗的 PI3K/AKT 信号通路抑制剂。然而，米替福新对男性生育力的影响尚未被充分了解。因此，本研究旨在探讨米替福新在顶体反应期间对精子功能的影响。杜洛克精子暴露于 0、2.5、5、10、20、40 和 80μM 米替福新并诱导顶体反应。结果表明，米替福新显著增加了 PI3K/AKT 信号通路相关蛋白的表达。米替福新显著抑制精子运动、运动动力学、顶体反应和酪氨酸磷酸化。然而，细胞内 ATP 水平和细胞活力没有显著影响。我们的研究结果表明，米替福新可能通过异常增加 PI3K/AKT 信号通路相关蛋白的水平来破坏精子功能。因此，在使用这种药物时，应考虑米替福新对男性生殖的有害影响。
