Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Department of Biotechnology, Inland Norway University of Applied Sciences, Hamar, Norway.
Mol Reprod Dev. 2021 Mar;88(3):187-200. doi: 10.1002/mrd.23461. Epub 2021 Feb 26.
In this study, the complexity of chromatin integrity was investigated in frozen-thawed semen samples from 37 sires with contrasting fertility, expressed as 56-day non-return rates (NR56). Protamine deficiency, thiols, and disulfide bonds were assessed and compared with previously published data for DNA fragmentation index (DFI) and high DNA stainability (HDS). In addition, in vitro embryo development and sperm DNA methylation were assessed using semen samples from 16 of these bulls. The percentages of DFI and HDS were negatively associated with NR56 and cleavage rate and positively associated with sperm protamine deficiency (p < 0.05). Significant differences in cleavage and blastocyst rates were observed between bulls of high and low NR56. However, once fertilization occurred, further development into blastocysts was not associated with NR56. The differential methylation analysis showed that spermatozoa from bulls of low NR56 were hypermethylated compared to bulls of high NR56. Pathway analysis showed that genes annotated to differentially methylated cytosines could participate in different biological pathways and have important biological roles related to bull fertility. In conclusion, sperm cells from Norwegian Red bulls of inferior fertility have less compact chromatin structure, higher levels of DNA damage, and are hypermethylated compared with bulls of superior fertility.
在这项研究中,我们研究了来自 37 头具有不同繁殖力公牛的冷冻-解冻精液样本中染色质完整性的复杂性,繁殖力以 56 天的受胎率(NR56)来表示。我们评估了鱼精蛋白缺乏、巯基和二硫键,并与先前发表的 DNA 碎片指数(DFI)和高 DNA 染色性(HDS)数据进行了比较。此外,我们还使用其中 16 头公牛的精液样本评估了体外胚胎发育和精子 DNA 甲基化。DFI 和 HDS 的百分比与 NR56、卵裂率呈负相关,与精子鱼精蛋白缺乏呈正相关(p<0.05)。高和低 NR56 公牛之间的卵裂和囊胚率存在显著差异。然而,一旦发生受精,进一步发育成囊胚与 NR56 无关。差异甲基化分析显示,NR56 较低的公牛的精子与 NR56 较高的公牛的精子相比,甲基化程度更高。通路分析表明,注释为差异甲基化胞嘧啶的基因可能参与不同的生物学途径,并具有与公牛繁殖力相关的重要生物学作用。总之,与繁殖力较高的公牛相比,繁殖力较低的挪威红牛精子的染色质结构更不紧凑,DNA 损伤水平更高,并且甲基化程度更高。