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探索精子的表观遗传景观：氧化应激和抗氧化剂补充对DNA甲基化和羟甲基化的影响。

Exploring the Epigenetic Landscape of Spermatozoa: Impact of Oxidative Stress and Antioxidant Supplementation on DNA Methylation and Hydroxymethylation.

作者信息

Hug Elisa, Renaud Yoan, Guiton Rachel, Ben Sassi Mehdi, Marcaillou Charles, Moazamian Aron, Gharagozloo Parviz, Drevet Joël R, Saez Fabrice

机构信息

GReD Institute, Université Clermont Auvergne, Faculté de Médecine, CRBC, 28 Place Henri Dunant, 63001 Clermont-Ferrand, France.

EVALSEM, Clermont Auvergne Innovation, Université Clermont Auvergne, Faculté de Médecine, CRBC, 28 Place Henri Dunant, 63001 Clermont-Ferrand, France.

出版信息

Antioxidants (Basel). 2024 Dec 12;13(12):1520. doi: 10.3390/antiox13121520.

DOI:10.3390/antiox13121520
PMID:39765848
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11726892/
Abstract

Reproductive success is dependent on gamete integrity, and oxidative stress alters male nuclei, meaning that no DNA repair is possible due to chromatin compaction. The composition of sperm makes it highly sensitive to reactive oxygen species (ROS) but, at the same time, ROS are needed for sperm physiology. Over the past 30 years, much attention has been paid to the consequences of oxidative stress on sperm properties and the protective effects of antioxidant formulations to help fertility. Spermatozoa also carry epigenetic marks, critical for embryo development and the health of offspring. As DNA oxidative damage may disturb the sperm epigenome, we used an established mouse model of post-testicular sperm DNA oxidation to investigate sperm DNA methylation and hydroxymethylation. We also analyzed the potential corrective effect of oral antioxidant supplementation, proven to reduce sperm DNA oxidative damage, on sperm DNA methyl/hydroxymethyl marks. We show that sperm DNA oxidation is associated with a significant increase in overall hydroxymethylation. Oral antioxidant supplementation led to unexpected mild epigenetic changes. Antioxidant supplementation should not be proposed without proper clinical evaluation as it may alter sperm epigenetic marks, leading to a risk of paternally inherited epigenetic alterations.

摘要

生殖成功取决于配子的完整性，而氧化应激会改变雄性细胞核，这意味着由于染色质压缩，DNA无法进行修复。精子的组成使其对活性氧（ROS）高度敏感，但与此同时，精子生理功能又需要ROS。在过去30年里，氧化应激对精子特性的影响以及抗氧化剂配方对生育能力的保护作用受到了广泛关注。精子还携带表观遗传标记，这对胚胎发育和后代健康至关重要。由于DNA氧化损伤可能会扰乱精子表观基因组，我们使用了一种已建立的睾丸后精子DNA氧化小鼠模型来研究精子DNA甲基化和羟甲基化。我们还分析了口服抗氧化剂补充剂（已证明可减少精子DNA氧化损伤）对精子DNA甲基/羟甲基标记的潜在纠正作用。我们发现精子DNA氧化与整体羟甲基化的显著增加有关。口服抗氧化剂补充剂导致了意想不到的轻微表观遗传变化。在没有适当临床评估的情况下，不应建议补充抗氧化剂，因为它可能会改变精子表观遗传标记，导致父系遗传表观遗传改变的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b06c/11726892/97164bc62e4e/antioxidants-13-01520-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b06c/11726892/77f136b878c8/antioxidants-13-01520-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b06c/11726892/f72ceaab2b0e/antioxidants-13-01520-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b06c/11726892/0820bde1f095/antioxidants-13-01520-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b06c/11726892/ce443483ac2d/antioxidants-13-01520-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b06c/11726892/3885ec5f9228/antioxidants-13-01520-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b06c/11726892/f3f9f3e5a179/antioxidants-13-01520-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b06c/11726892/97164bc62e4e/antioxidants-13-01520-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b06c/11726892/77f136b878c8/antioxidants-13-01520-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b06c/11726892/f72ceaab2b0e/antioxidants-13-01520-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b06c/11726892/0820bde1f095/antioxidants-13-01520-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b06c/11726892/ce443483ac2d/antioxidants-13-01520-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b06c/11726892/3885ec5f9228/antioxidants-13-01520-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b06c/11726892/f3f9f3e5a179/antioxidants-13-01520-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b06c/11726892/97164bc62e4e/antioxidants-13-01520-g007.jpg

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