Perrier Jean-Philippe, Kenny David A, Chaulot-Talmon Aurélie, Byrne Colin J, Sellem Eli, Jouneau Luc, Aubert-Frambourg Anne, Schibler Laurent, Jammes Hélène, Lonergan Patrick, Fair Sean, Kiefer Hélène
Laboratory of Animal Reproduction, Department of Biological Sciences, Biomaterials Research Cluster, Bernal Institute, University of Limerick, Limerick, Ireland.
Animal and Bioscience Research Department, Animal and Grassland Research and Innovation Centre, Teagasc, Grange, Co. Meath, Ireland.
Front Genet. 2020 Aug 26;11:945. doi: 10.3389/fgene.2020.00945. eCollection 2020.
In humans and model species, alterations of sperm DNA methylation patterns have been reported in cases of spermatogenesis defects, male infertility and exposure to toxins or nutritional challenges, suggesting that a memory of environmental or physiological changes is recorded in the sperm methylome. The objective of this study was to ascertain if early life plane of nutrition could have a latent effect on DNA methylation patterns in sperm produced post-puberty. Holstein-Friesian calves were assigned to either a high (H) or moderate (M) plane of nutrition for the first 24 weeks of age, then reassigned to the M diet until puberty, resulting in HM and MM groups. Sperm DNA methylation patterns from contrasted subgroups of bulls in the HM (ejaculates recovered at 15 months of age; = 9) and in the MM (15 and 16 months of age; = 7 and 9, respectively) were obtained using Reduced Representation Bisulfite Sequencing. Both 15 and 16 months were selected in the MM treatment as these bulls reached puberty approximately 1 month after the HM bulls. Hierarchical clustering demonstrated that inter-individual variability unrelated to diet or age dominated DNA methylation profiles. While the comparison between 15 and 16 months of age revealed almost no change, 580 differentially methylated CpGs (DMCs) were identified between the HM and MM groups. Differentially methylated CpGs were mostly hypermethylated in the HM group, and enriched in endogenous retrotransposons, introns, intergenic regions, and shores and shelves of CpG islands. Furthermore, genes involved in spermatogenesis, Sertoli cell function, and the hypothalamic-pituitary-gonadal axis were targeted by differential methylation when HM and MM groups were compared at 15 months of age, reflecting the earlier timing of puberty onset in the HM bulls. In contrast, the genes still differentially methylated in MM bulls at 16 months of age were enriched for ATP-binding molecular function, suggesting that changes to the sperm methylome could persist even after the HM and MM bulls reached a similar level of sexual maturity. Together, results demonstrate that enhanced plane of nutrition in pre-pubertal calves associated with advanced puberty induced modest but persistent changes in sperm DNA methylation profiles after puberty.
在人类和模式生物中，已有报道称在精子发生缺陷、男性不育以及接触毒素或营养挑战的情况下，精子DNA甲基化模式会发生改变，这表明环境或生理变化的记忆记录在精子甲基化组中。本研究的目的是确定生命早期的营养水平是否会对青春期后产生的精子中的DNA甲基化模式产生潜在影响。荷斯坦 - 弗里生犊牛在出生后的前24周被分配到高营养水平（H）或中等营养水平（M）组，然后重新分配到M组饮食直至青春期，从而形成HM组和MM组。使用简化代表性亚硫酸氢盐测序获得了HM组（15月龄采集的精液；n = 9）和MM组（15月龄和16月龄；分别为n = 7和9）中对比亚组公牛的精子DNA甲基化模式。在MM组中选择了15月龄和16月龄，因为这些公牛比HM组公牛大约晚1个月达到青春期。层次聚类表明，与饮食或年龄无关的个体间变异性主导了DNA甲基化谱。虽然15月龄和16月龄之间的比较几乎没有变化，但在HM组和MM组之间鉴定出580个差异甲基化的CpG（DMC）。差异甲基化的CpG在HM组中大多是高甲基化的，并且在内源逆转录转座子、内含子、基因间区域以及CpG岛的边缘和侧翼区域富集。此外，在15月龄比较HM组和MM组时，参与精子发生、支持细胞功能以及下丘脑 - 垂体 - 性腺轴的基因被差异甲基化靶向，这反映了HM组公牛青春期开始时间更早。相比之下，16月龄的MM组公牛中仍存在差异甲基化的基因在ATP结合分子功能方面富集，这表明即使HM组和MM组公牛达到相似的性成熟水平后，精子甲基化组的变化仍可能持续。总之，结果表明青春期前犊牛营养水平的提高与青春期提前相关，会在青春期后诱导精子DNA甲基化谱发生适度但持续的变化。
