DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage
DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage
复制标题
DOI：
10.1016/j.dnarep.2007.12.011
复制
发表时间：
2008-04-02
期刊：
影响因子：
3.8
通讯作者：
Wyrobek, Andrew J.
中科院分区：
文献类型：
--
作者：
Marchetti, Francesco;Wyrobek, Andrew J.
小鼠精子发生（精子发生）的减数分裂后阶段对环境诱变剂的基因组效应非常敏感，因为当雄性生殖细胞形成成熟精子时，它们逐渐失去修复DNA损伤的能力。我们假设，在修复缺陷阶段反复暴露于诱变剂会导致小鼠精子中可遗传基因组损伤的积累，从而导致受精后受精卵中的染色体畸变。我们使用单次或分次暴露于烟草烟雾的一种成分二环氧丁烷 (DEB) 的组合，来研究精子发生 3 周期间 DNA 修复效率的差异如何影响早期精子细胞（受精前 21-15 天 (dbf)）、晚期精子细胞 (14-8 dbf) 和精子 (7-1 dbf) 中 DEB 诱导的遗传性损伤的积累。使用 PAINT/DAPI 对合子中期染色体畸变的分析表明，晚期精子细胞和精子无法修复 DEB 诱导的 DNA 损伤，如显着增加所证明的那样 (P
The postmeiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the 3 weeks of spermiogenesis affected the accumulation of DEB-induced heritable damage in early spermatids (21-15 days before fertilization (dbf)), late spermatids (14-8 dbf) and sperm (7-1 dbf). Analysis of chromosomal aberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P