Mitochondrial function and reactive oxygen species production during human sperm capacitation: Unraveling key players

电容 精子 线粒体 活性氧 抗霉素A 生物 细胞生物学 生物化学 超氧化物 氧化磷酸化 化学 男科 遗传学 医学
作者
Pilar Irigoyen,Santiago Mansilla,Laura Castro,Adriana Cassina,Rossana Sapiro
出处
期刊:The FASEB Journal [Wiley]
卷期号:38 (4) 被引量:4
标识
DOI:10.1096/fj.202301957rr
摘要

Abstract Sperm capacitation is a critical process for male fertility. It involves a series of biochemical and physiological changes that occur in the female reproductive tract, rendering the sperm competent for successful fertilization. The precise mechanisms and, specifically, the role of mitochondria, in sperm capacitation remain incompletely understood. Previously, we revealed that in mouse sperm mitochondrial activity (e.g., oxygen consumption, membrane potential, ATP/ADP exchange, and mitochondrial Ca 2+ ) increases during capacitation. Herein, we studied mitochondrial function by high‐resolution respirometry (HRR) and reactive oxygen species production in capacitated (CAP) and non‐capacitated (NC) human spermatozoa. We found that in capacitated sperm from normozoospermic donors, the respiratory control ratio increased by 36%, accompanied by a double oxygen consumption rate (OCR) in the presence of antimycin A. Extracellular hydrogen peroxide (H 2 O 2 ) detection was three times higher in CAP than in NC sperm cells. To confirm that H 2 O 2 production depends on mitochondrial superoxide () formation, we evaluated mitochondrial aconitase (ACO2) amount, activity, and role in the metabolic flux from the sperm tricarboxylic acid cycle. We estimated that CAP cells produce, on average by individual, (59 ± 22)% more in the steady‐state compared to NC cells. Finally, we analyzed two targets of oxidative stress: lipid peroxidation by western blot against 4‐hydroxynonenal and succinate dehydrogenase (SDH) activity by HRR. We did not observe modifications in lipoperoxidation nor the activity of SDH, suggesting that during capacitation, the increase in mitochondrial H 2 O 2 production does not damage sperm and it is necessary for the normal CAP process.
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