Sumbalová Zuzana, Rausová Zuzana, Kucharská Jarmila, Šranko Patrik, Harbulák Peter, Svitok Pavel, López-Lluch Guillermo, Gvozdjáková Anna
Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University Bratislava, Sasinkova 2, 811 08 Bratislava, Slovakia.
Pharmacobiochemical Laboratory of 3rd Department of Internal Medicine, Faculty of Medicine, Comenius University Bratislava, Sasinkova 4, 811 08 Bratislava, Slovakia.
Int J Mol Sci. 2024 Dec 31;26(1):268. doi: 10.3390/ijms26010268.
Fertility disorders are a worldwide problem affecting 8-12% of the population, with the male factor substantially contributing to about 40-50% of all infertility cases. Mitochondria, crucial organelles for cellular viability, play a pivotal role in the processes of spermatogenesis and significantly affect sperm quality and their fertilizing ability. Mitochondrial oxidative phosphorylation (OXPHOS) dysfunction, reduced energy supply for sperm, reduced endogenous coenzyme Q (CoQ) levels, and oxidative stress are among the main factors that contribute to male infertility. There is great interest in the role of mitochondrial dysfunction in male infertility, and the diagnosis and assessment of mitochondrial health in infertile men present challenges. Platelets are a source of viable mitochondria that can be obtained non-invasively. Changes in platelet mitochondrial respiration were documented in various diseases, confirming platelet mitochondrial bioenergetics as a marker of systemic mitochondrial health. The aim of our study was to determine whether (a) platelet mitochondrial bioenergetics and CoQ levels could be used as metabolic markers of mitochondrial health in infertile men and whether (b) the parameters of mitochondrial respiration in platelets correlate with sperm parameters. The high-resolution respirometry method was used for platelet bioenergetics, and the high-performance liquid chromatography (HPLC) method was used for CoQ level measurement. The static oxidation-reduction potential (sORP) of the ejaculate was evaluated by MiOXSYSSystem. We found a deficit in mitochondrial complex I-linked OXPHOS and electron transfer capacity and CoQ and α-tocopherol levels in infertile men. The proportion of sperm, heads, and midpiece abnormalities correlated negatively with the complex I-linked parameters of platelet mitochondrial bioenergetics. We suppose that dysfunctional mitochondria contribute to increased oxidative stress, and these imbalances can be considered a cause of Male Oxidative Stress Infertility (MOSI). Our results suggest that platelet mitochondrial function and the endogenous levels of CoQ in platelets could be used as metabolic markers for monitoring mitochondrial health and targeted therapy in infertile men. sORP could be a useful clinical biomarker of MOSI.
生育障碍是一个全球性问题，影响着8%至12%的人口，其中男性因素在所有不孕病例中约占40%至50%。线粒体是细胞生存能力的关键细胞器，在精子发生过程中起关键作用，并显著影响精子质量及其受精能力。线粒体氧化磷酸化（OXPHOS）功能障碍、精子能量供应减少、内源性辅酶Q（CoQ）水平降低以及氧化应激是导致男性不育的主要因素。线粒体功能障碍在男性不育中的作用备受关注，而不育男性线粒体健康的诊断和评估面临挑战。血小板是可无创获取的有活力线粒体的来源。在各种疾病中都记录到了血小板线粒体呼吸的变化，证实血小板线粒体生物能量学是全身线粒体健康的一个指标。我们研究的目的是确定：（a）血小板线粒体生物能量学和CoQ水平是否可用作不育男性线粒体健康的代谢指标，以及（b）血小板中线粒体呼吸参数是否与精子参数相关。采用高分辨率呼吸测定法检测血小板生物能量学，采用高效液相色谱（HPLC）法测定CoQ水平。通过MiOXSYSSystem评估射精的静态氧化还原电位（sORP）。我们发现不育男性线粒体复合体I相关的OXPHOS和电子传递能力以及CoQ和α-生育酚水平存在缺陷。精子头部和中段异常的比例与血小板线粒体生物能量学的复合体I相关参数呈负相关。我们推测功能失调的线粒体导致氧化应激增加，这些失衡可被视为男性氧化应激性不育（MOSI）的一个原因。我们的结果表明，血小板线粒体功能和血小板中CoQ的内源性水平可用作监测不育男性线粒体健康和靶向治疗的代谢指标。sORP可能是MOSI的一个有用的临床生物标志物。
