Effect of Antioxidant Supplementation on the Sperm Proteome of Idiopathic Infertile Men
Effect of Antioxidant Supplementation on the Sperm Proteome of Idiopathic Infertile Men
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DOI：
10.3390/antiox8100488
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发表时间：
2019-10-01
期刊：
影响因子：
7
通讯作者：
Sharma, Rakesh
中科院分区：
文献类型：
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作者：
Agarwal, Ashok;Selvam, Manesh Kumar Panner;Sharma, Rakesh
在特发性男性不育患者中补充抗氧化剂对精液参数有有益的影响。然而，这种效应背后的分子机制还没有报道。这项研究的目的是评估特发性不育男性补充抗氧化剂前后的精子蛋白质组。特发性不孕症患者每天服用一次抗氧化剂，为期6个月。在抗氧化剂治疗前后患者之间的379个差异表达蛋白(DEP)中，大多数蛋白(n=274)在抗氧化剂治疗后过度表达。生物信息学分析揭示了氧化磷酸化途径的激活和参与精子发生、精子成熟、精子结合、受精和正常生殖功能的关键蛋白的上调。此外，与抗氧化防御系统(PPARGC1A)和自由基清除(NFE2L2)相关的转录因子在治疗后被预测为功能激活。经Western印迹验证的关键DEPS，即NDUFS1、CCT3、PRKARA1和SPA17在治疗后均有明显的高表达。我们新的蛋白质组学发现表明，在特发性不育男性中补充抗氧化剂可以在分子水平上改善精子功能，这是通过调节参与CREM信号、线粒体功能和蛋白质氧化的蛋白质来实现的。此外，TIRE复合体的激活有助于核致密，维持端粒长度，鞭毛功能，以及精子-卵母细胞相互作用的透明带受体的表达。
Antioxidant supplementation in idiopathic male infertility has a beneficial effect on semen parameters. However, the molecular mechanism behind this effect has not been reported. The objective of this study was to evaluate the sperm proteome of idiopathic infertile men pre- and post-antioxidant supplementation. Idiopathic infertile men were provided with oral antioxidant supplementation once daily for a period of 6 months. Of the 379 differentially expressed proteins (DEPs) between pre- and post-antioxidant treatment patients, the majority of the proteins (n = 274) were overexpressed following antioxidant treatment. Bioinformatic analysis revealed the activation of oxidative phosphorylation pathway and upregulation of key proteins involved in spermatogenesis, sperm maturation, binding of sperm, fertilization and normal reproductive function. In addition, the transcriptional factors associated with antioxidant defense system (PPARGC1A) and free radical scavenging (NFE2L2) were predicted to be functionally activated post-treatment. Key DEPs, namely, NDUFS1, CCT3, PRKARA1 and SPA17 validated by Western blot showed significant overexpression post-treatment. Our novel proteomic findings suggest that antioxidant supplementation in idiopathic infertile men improves sperm function at the molecular level by modulating proteins involved in CREM signaling, mitochondrial function and protein oxidation. Further, activation of TRiC complex helped in nuclear compaction, maintenance of telomere length, flagella function, and expression of zona pellucida receptors for sperm-oocyte interaction.