Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans
Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans
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DOI：
10.1016/j.cmet.2015.11.004
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发表时间：
2016-02-09
期刊：
影响因子：
29
通讯作者：
Barres, Romain
中科院分区：
文献类型：
--
作者：
Donkin, Ida;Versteyhe, Soetkin;Barres, Romain
肥胖是一种遗传性疾病，肥胖父亲的孩子患肥胖症的风险更高。环境因素的表观遗传影响体细胞组织，但这些因素的贡献，在人类配子的表观遗传模式的建立是未知的。在这里，我们假设体重减轻重塑了人类肥胖症精子的表观遗传特征。对瘦男性和肥胖男性精子表观基因组的综合分析显示，组蛋白定位相似，但小的非编码RNA表达和DNA甲基化模式明显不同。在一个单独的病态肥胖男性队列中，手术引起的体重减轻与精子DNA甲基化的急剧重塑有关，特别是在涉及食欲中枢控制的遗传位置。我们的数据提供的证据表明，人类精子的表观基因组在环境压力下动态变化，并提供了深入了解肥胖如何可能传播代谢功能障碍到下一代。
Obesity is a heritable disorder, with children of obese fathers at higher risk of developing obesity. Environmental factors epigenetically influence somatic tissues, but the contribution of these factors to the establishment of epigenetic patterns in human gametes is unknown. Here, we hypothesized that weight loss remodels the epigenetic signature of spermatozoa in human obesity. Comprehensive profiling of the epigenome of sperm from lean and obese men showed similar histone positioning, but small non-coding RNA expression and DNA methylation patterns were markedly different. In a separate cohort of morbidly obese men, surgery-induced weight loss was associated with a dramatic remodeling of sperm DNA methylation, notably at genetic locations implicated in the central control of appetite. Our data provide evidence that the epigenome of human spermatozoa dynamically changes under environmental pressure and offers insight into how obesity may propagate metabolic dysfunction to the next generation.