Department of Biological Sciences, Laboratory of Animal Reproduction, Biomaterials Research Cluster, Bernal Institute, Faculty of Science and Engineering, University of Limerick, Limerick, Ireland.
Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France.
BMC Genomics. 2022 May 18;23(1):379. doi: 10.1186/s12864-022-08614-5.
Despite a multifactorial approach being taken for the evaluation of bull semen quality in many animal breeding centres worldwide, reliable prediction of bull fertility is still a challenge. Recently, attention has turned to molecular mechanisms, which could uncover potential biomarkers of fertility. One of these mechanisms is DNA methylation, which together with other epigenetic mechanisms is essential for the fertilising sperm to drive normal embryo development and establish a viable pregnancy. In this study, we hypothesised that bull sperm DNA methylation patterns are related to bull fertility. We therefore investigated DNA methylation patterns from bulls used in artificial insemination with contrasting fertility scores.
The DNA methylation patterns were obtained by reduced representative bisulphite sequencing from 10 high-fertility bulls and 10 low-fertility bulls, having average fertility scores of - 6.6 and + 6.5%, respectively (mean of the population was zero). Hierarchical clustering analysis did not distinguish bulls based on fertility but did highlight individual differences. Despite this, using stringent criteria (DNA methylation difference ≥ 35% and a q-value < 0.001), we identified 661 differently methylated cytosines (DMCs). DMCs were preferentially located in intergenic regions, introns, gene downstream regions, repetitive elements, open sea, shores and shelves of CpG islands. We also identified 10 differently methylated regions, covered by 7 unique genes (SFRP1, STXBP4, BCR, PSMG4, ARSG, ATP11A, RXRA), which are involved in spermatogenesis and early embryonic development.
This study demonstrated that at specific CpG sites, sperm DNA methylation status is related to bull fertility, and identified seven differently methylated genes in sperm of subfertile bulls that may lead to altered gene expression and potentially influence embryo development.
尽管在世界上许多动物繁殖中心都采用了多因素方法来评估公牛精液质量，但可靠地预测公牛的生育能力仍然是一个挑战。最近，人们的注意力转向了分子机制，这些机制可能揭示出潜在的生育能力生物标志物。其中一种机制是 DNA 甲基化，它与其他表观遗传机制一起，对于使受精精子驱动正常胚胎发育和建立可行的妊娠至关重要。在这项研究中，我们假设公牛精子 DNA 甲基化模式与公牛的生育能力有关。因此，我们调查了具有不同生育能力评分的人工授精中使用的公牛的精子 DNA 甲基化模式。
通过对 10 头高生育能力公牛和 10 头低生育能力公牛的代表性还原亚硫酸氢盐测序，获得了 DNA 甲基化模式，它们的平均生育能力评分分别为-6.6 和+6.5%（群体平均值为零）。层次聚类分析不能根据生育能力区分公牛，但确实突出了个体差异。尽管如此，使用严格的标准（DNA 甲基化差异≥35%，q 值<0.001），我们确定了 661 个不同甲基化的胞嘧啶（DMC）。DMC 优先位于基因间区、内含子、基因下游区、重复元件、开放海、CpG 岛的海岸和支架。我们还鉴定了 10 个不同甲基化的区域，由 7 个独特的基因（SFRP1、STXBP4、BCR、PSMG4、ARSG、ATP11A、RXRA）覆盖，这些基因参与精子发生和早期胚胎发育。
本研究表明，在特定的 CpG 位点，精子 DNA 甲基化状态与公牛的生育能力有关，并在生育力低下的公牛精子中鉴定出 7 个不同甲基化的基因，这些基因可能导致基因表达的改变，并可能影响胚胎发育。
