Nowicka-Bauer Karolina, Nixon Brett
Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland.
Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, Newcastle, NSW 2308, Australia.
Antioxidants (Basel). 2020 Feb 4;9(2):134. doi: 10.3390/antiox9020134.
A state of oxidative stress (OS) and the presence of reactive oxygen species (ROS) in the male reproductive tract are strongly correlated with infertility. While physiological levels of ROS are necessary for normal sperm functioning, elevated ROS production can overwhelm the cell's limited antioxidant defenses leading to dysfunction and loss of fertilizing potential. Among the deleterious pleiotropic impacts arising from OS, sperm motility appears to be particularly vulnerable. Here, we present a mechanistic account for how OS contributes to altered sperm motility profiles. In our model, it is suggested that the abundant polyunsaturated fatty acids (PUFAs) residing in the sperm membrane serve to sensitize the male germ cell to ROS attack by virtue of their ability to act as substrates for lipid peroxidation (LPO) cascades. Upon initiation, LPO leads to dramatic remodeling of the composition and biophysical properties of sperm membranes and, in the case of the mitochondria, this manifests in a dissipation of membrane potential, electron leakage, increased ROS production and reduced capacity for energy production. This situation is exacerbated by the production of cytotoxic LPO byproducts such as 4-hydroxynonenal, which dysregulate molecules associated with sperm bioenergetic pathways as well as the structural and signaling components of the motility apparatus. The impact of ROS also extends to lesions in the paternal genome, as is commonly seen in the defective spermatozoa of asthenozoospermic males. Concluding, the presence of OS in the male reproductive tract is strongly and positively correlated with reduced sperm motility and fertilizing potential, thus providing a rational target for the development of new therapeutic interventions.
男性生殖道中的氧化应激（OS）状态和活性氧（ROS）的存在与不育密切相关。虽然ROS的生理水平对于正常精子功能是必要的，但ROS产生的增加会使细胞有限的抗氧化防御能力不堪重负，导致功能障碍和受精潜力丧失。在OS产生的多种有害影响中，精子活力似乎特别容易受到影响。在这里，我们阐述了OS如何导致精子活力改变的机制。在我们的模型中，有人提出精子膜中丰富的多不饱和脂肪酸（PUFA）因其能够作为脂质过氧化（LPO）级联反应的底物，从而使雄性生殖细胞对ROS攻击敏感。一旦启动，LPO会导致精子膜的组成和生物物理特性发生显著重塑，就线粒体而言，这表现为膜电位耗散、电子泄漏、ROS产生增加以及能量产生能力降低。细胞毒性LPO副产物如4-羟基壬烯醛的产生会加剧这种情况，这些副产物会使与精子生物能量途径相关的分子以及运动装置的结构和信号成分失调。ROS的影响还延伸到父本基因组中的损伤，这在弱精子症男性的缺陷精子中很常见。总之，男性生殖道中OS的存在与精子活力降低和受精潜力密切正相关，因此为开发新的治疗干预措施提供了合理的靶点。
