在精子电容化过程中,miltefosine通过改变PI3K/AKT信号通路来诱导生殖毒性
Eun-Ju Jung1, Woo-Jin Lee1, Jeong-Won Bae1
1Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Gyeongsangbuk-do 37224, Republic of Korea.
Environmental toxicology and pharmacology
|September 12, 2024
概括
用于莱什曼病和癌症的米尔特福辛通过破坏PI3K/AKT通路来损害精子功能. 这种药物对精子运动和容量产生负面影响,引发了对男性生育能力的担忧.
科学领域:
- 生殖生物学 生殖生物学
- 药理学 药理学是指药理学的学科.
- 细胞信号传递 细胞信号传递
背景情况:
- 米尔特福辛是莱什曼病的关键药物,并研究了抗癌/抗病毒用途.
- 它对男性生育能力的影响在很大程度上仍未被描述.
- PI3K/AKT信号通路对于各种细胞过程至关重要,包括精子功能.
研究的目的:
- 为了研究米尔特福辛在容量化过程中对精子功能的影响.
- 阐明PI3K/AKT信号通路在miltefosine诱导的精子对精子的影响中的作用.
主要方法:
- 杜洛克精子被用不同度的密尔特福辛 (0-80μM) 治疗.
- 在暴露于米尔特福辛后诱导了精子电容.
- 评估的关键参数包括精子运动性,动力学,电容性,氨酸酸化,细胞内ATP和细胞活力.
主要成果:
- 米尔特福辛显著增加了PI3K/AKT通路相关蛋白质的表达.
- 精子运动性,运动动力学,电容和氨酸酸化明显抑制.
- 细胞内ATP水平和精子活力不受米尔特福辛治疗的影响.
结论:
- 米尔特福辛破坏了正常的精子功能,可能是由于PI3K/AKT信号通路的异常激活.
- 这些发现突出了米尔特福辛对男性生殖健康的潜在不良影响.
- 在临床应用过程中,需要考虑米尔特福辛对男性生育能力的影响.
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