Male obesity impacts DNA methylation reprogramming in sperm.
Male obesity impacts DNA methylation reprogramming in sperm.
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男性肥胖影响精子DNA甲基化重编程
DOI：
10.1186/s13148-020-00997-0
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发表时间：
2021-01-25
影响因子：
5.7
通讯作者：
Murphy SK
中科院分区：
文献类型：
--
作者：
Keyhan S;Burke E;Schrott R;Huang Z;Grenier C;Price T;Raburn D;Corcoran DL;Soubry A;Hoyo C;Murphy SK
男性肥胖对发病率和死亡率有着深远的影响，但人们对肥胖对配子的影响以及男性肥胖对下一代的潜在负面影响知之甚少。DNA甲基化有助于基因调控，并在配子体发生过程中被消除和重新建立。在整个青春期后的精子发生过程中，即使在附睾成熟期间，也需要持续保持已建立的甲基化和完整的DNA甲基化编程。这种动态的表观遗传景观可能会增加对环境影响的脆弱性，包括可能破坏重编程保真度的致肥环境。在这里，我们进行了一项探索性分析，表明超重/肥胖（n = 20）与成熟精子DNA甲基化谱的差异相关，相对于正常BMI的对照组（n = 47）。我们使用Infinium HumanMethylation450 BeadChips在人类精子中鉴定出3264个与BMI显著相关的CpG位点（p < 0.05）。这些CpG位点在涉及癌症、神经系统发育和干细胞多能性的转录调控和错误调控的基因中被显著地过度代表。使用亚硫酸酯对克隆等位基因进行测序对单个精子进行分析，发现甲基化差异存在于精子的一个子集中，而不是随机分布在所有精子中。男性肥胖与精子DNA甲基化谱的改变有关，这似乎影响了精子子集的重编程保真度，暗示了对精原细胞的影响。需要进一步的工作来确定这些DNA甲基化改变的潜在遗传性。如果是遗传的，这些变化有可能阻碍正常的发育。
Male obesity has profound effects on morbidity and mortality, but relatively little is known about the impact of obesity on gametes and the potential for adverse effects of male obesity to be passed to the next generation. DNA methylation contributes to gene regulation and is erased and re-established during gametogenesis. Throughout post-pubertal spermatogenesis, there are continual needs to both maintain established methylation and complete DNA methylation programming, even during epididymal maturation. This dynamic epigenetic landscape may confer increased vulnerability to environmental influences, including the obesogenic environment, that could disrupt reprogramming fidelity. Here we conducted an exploratory analysis that showed that overweight/obesity (n = 20) is associated with differences in mature spermatozoa DNA methylation profiles relative to controls with normal BMI (n = 47). We identified 3264 CpG sites in human sperm that are significantly associated with BMI (p < 0.05) using Infinium HumanMethylation450 BeadChips. These CpG sites were significantly overrepresented among genes involved in transcriptional regulation and misregulation in cancer, nervous system development, and stem cell pluripotency. Analysis of individual sperm using bisulfite sequencing of cloned alleles revealed that the methylation differences are present in a subset of sperm rather than being randomly distributed across all sperm. Male obesity is associated with altered sperm DNA methylation profiles that appear to affect reprogramming fidelity in a subset of sperm, suggestive of an influence on the spermatogonia. Further work is required to determine the potential heritability of these DNA methylation alterations. If heritable, these changes have the potential to impede normal development.
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DOI：
10.1126/science.1229277
发表时间：
2013-01-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hackett JA;Sengupta R;Zylicz JJ;Murakami K;Lee C;Down TA;Surani MA
通讯作者：
Surani MA
影响因子：
3.7
作者：
McPherson NO;Bakos HW;Owens JA;Setchell BP;Lane M
通讯作者：
Lane M
DOI：
10.1016/b978-0-12-812433-8.00007-1
发表时间：
2019-01-01
期刊：
TOXICOEPIGENETICS: CORE PRINCIPLES AND APPLICATIONS
影响因子：
--
作者：
Deyssenroth, Maya A.;Wright, Robert O.
通讯作者：
Wright, Robert O.
影响因子：
30.8
作者：
ARIEL, M;CEDAR, H;MCCARREY, J
通讯作者：
MCCARREY, J
影响因子：
3.5
作者：
Murphy SK;Erginer E;Huang Z;Visco Z;Hoyo C
通讯作者：
Hoyo C