Epigenetic abnormalities of the mouse paternal zygotic genome associated with microinsemination of round spermatids
Epigenetic abnormalities of the mouse paternal zygotic genome associated with microinsemination of round spermatids
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DOI：
10.1016/j.ydbio.2005.10.026
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发表时间：
2006-01-01
影响因子：
2.7
通讯作者：
Wakayama, T
中科院分区：
文献类型：
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作者：
Kishigami, S;Van Thuan, N;Wakayama, T
虽然圆形精子细胞注射可用于为不产生成熟精子的雄性产生后代，但这种程序后胚胎发生的成功率显著低于使用成熟精子的类似程序。这种差异背后的机制尚不清楚。在这项研究中，我们证明，不像正常的父亲的基因组，来自一个圆形精子细胞的父亲合子基因组是高度再甲基化后的第一次有丝分裂前。细长精子细胞的基因组表现出中等水平的DNA甲基化，在圆形精子细胞和成熟精子之间，这表明男性生殖细胞在精子发生的这一阶段获得了维持其在父本合子基因组中甲基化不足状态的能力。此外，受精卵与阿司他丁A治疗导致DNA甲基化显着减少，特别是在精子细胞来源的父亲基因组，除了由组蛋白H3的赖氨酸9三甲基化富集的着丝粒周围区域。这些数据提供了对表观遗传错误的深入了解，这些错误可能与未成熟精子产生的胚胎发育不良有关。(c)2005年爱思唯尔公司All rights reserved.
Although round spermatid injection can be used to create progeny for males who do not produce mature sperm, the rate of successful embryogenesis after such procedures is significantly lower than that for similar procedures using mature spermatozoa. The mechanisms underlying this difference are unknown. In this study, we demonstrate that, unlike the normal paternal genome, the paternal zygotic genome derived from a round spermatid is highly remethylated before first mitosis after demethylation. Genomes from elongated spermatids exhibited an intermediate level of DNA methylation, between those of round spermatids and mature spermatozoa, suggesting that the male germ cell acquires the ability to maintain its undermethylated state in the paternal zygotic genome during this phase of spermiogenesis. In addition, treatment of zygotes with trichostatin A led to a significant reduction in DNA methylation, specifically in the spermatid-derived paternal genome, except for the pericentromeric regions enriched by trimethylation of Lys9 of histone H3. These data provide insight into epigenetic errors that may be associated with the poor development of embryos generated from immature spermatozoa. (c) 2005 Elsevier Inc. All rights reserved.