高血糖症,糖尿病(DM)的标志,是DM相关全身并发症的主要原因,包括生殖问题。此外,育龄男性的DM发病率日益受到关注,由于精子获能的复杂性(卵子受精的基本过程)超出了传统的精子参数,如计数,生存能力,和运动性。电容缺陷导致男性不育,DM相关的高血糖可能会影响这一过程。我们使用四氧嘧啶诱导的高血糖Wistar大鼠探索不受控制的高血糖对精子的影响。除了评估常规精子参数,我们还评估了功能指标,包括药理学方法的过度激活(HA),并通过计算机辅助精子分析(CASA)评估其效果;监测膜电位的荧光指标(EmR,DiSC3(5))和线粒体膜电位(Φ,JC-1);CatSper活动,利用其渗透Na+离子的能力,和ATP水平与荧光素-荧光素酶反应。我们用高血糖模型证实了以前的发现,这复制了传统精子参数的典型减少。在高血糖大鼠的精子中,我们观察到药物治疗后运动和HA水平增加。此外,CatSper活动不受高血糖的影响,而EmR在非获能条件下超极化。最后,我们注意到超极化Φ的百分比较低,ATP含量降低。本研究强调了高血糖对精子生理和获能影响的意义。我们提出低ATP水平会扰乱能量状态,信号通路,离子通道活动,运动性,和HA。我们的发现提供了对DM相关不孕症和潜在治疗策略的见解。
Hyperglycemia, the hallmark of diabetes mellitus (DM), is the main cause of DM-related systemic complications, including reproductive issues. Furthermore, the incidence of DM in males of reproductive ages is becoming an increasing concern, as the complexity of sperm capacitation (an essential process for fertilizing the egg) extends beyond conventional sperm parameters such as count, viability, and motility. Capacitation defects cause male infertility, and DM-related hyperglycemia may affect this process. We explore the effects of uncontrolled hyperglycemia on sperm using alloxan-induced hyperglycemic Wistar rats. In addition to assessing conventional sperm parameters, we also evaluated functional indicators, including hyperactivation (HA) with a pharmacological approach and assessed its effects with a computer-assisted sperm analysis (CASA); fluorescence indicators to monitor membrane potential (EmR, DiSC3(5)) and mitochondrial membrane potential (Ψ, JC-1); CatSper activity, using its ability to permeate Na+ ions, and ATP levels with the luciferin-luciferase reaction. We confirmed previous findings with our hyperglycemic model, which replicated the typical reduction on conventional sperm parameters. In sperm from hyperglycemic rats, we observed increased motility and HA levels after pharmacological treatment. Additionally, CatSper activity was unaffected by hyperglycemia, while EmR was hyperpolarized under non-capacitating condition. Finally, we noted a low percentage of hyperpolarized Ψ and reduced ATP content. This study highlights the significance of impact of hyperglycemia on sperm physiology and capacitation. We proposed that low ATP levels perturb energy state, signaling pathways, ion channels activity, motility, and HA. Our findings offer insight into DM-associated infertility and potential treatment strategies.