The relationship between fertility and mutation on genome caused by oxidative damage during spermatogenesis

精子发生过程中氧化损伤引起的基因组突变与生育能力的关系

• 批准号: 14571505
• 负责人: YOSHIMURA Yasuhide
• 金额: $ 2.24万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571505/
• 关键词: germ cell; spermatogenesis; oxidative DNA damage; DNA repair; fertility; 精巣; ミスマッチ修復; 放射線影響

We have studied about the relationship between fertility and mutation on genome caused by oxidative damage during spermatogenesis. We used C57BL/6 wild type mice as well as Msh2 deficient mice. We have observed the testis section according to the aging and also we performed irradiation. Irradiation should increase the oxidative DNA damage on the genome of germ cells. Testis was fixed with bouins solution and sectioned to 5μm. We also observed fertility of Msh2 deficient mice.Results : The testis weight of Msh2 deficient mice was decreased according to the age. After 14 weeks old, the testis weight of Msh2 deficient mice become 60% of wild type one. The observation of section reveals degeneration of gonia and pre leptotene stage. Durin gonia and pre leptotene stage, we could observe significant apoptotic germ cells. We supposed the decrease of testis weight should be caused by the continuous apoptosis of germ cells. Although the apoptotic germ cell number increase after 14 weeks old Msh2 deficient mice and the weight of the testis decrease to 60% of wild type mice, they reveals normal fertility.

我们研究了精子发生过程中氧化损伤引起的基因组突变与生育的关系。我们使用了C57BL/6野生型小鼠和Msh2基因缺陷小鼠。根据年龄对睾丸切片进行观察，并进行放射治疗。辐射可增加生殖细胞基因组DNA的氧化损伤。用肉汤固定小鼠睾丸，切片5μm，观察Msh2基因缺陷小鼠的生育力。结果：Msh2基因缺陷小鼠的睾丸重量随年龄增长而降低。14周龄后，Msh2基因缺陷小鼠的睾丸重量约为野生型的60%。切片观察可见神经节细胞变性，细线期前期。在卵泡期和细线期前期，我们可以观察到明显的生殖细胞凋亡。我们推测，睾丸重量的减轻可能是生殖细胞持续凋亡所致。虽然14周龄Msh2基因缺陷小鼠的生殖细胞凋亡数增加，睾丸重量减少到野生型小鼠的60%，但仍显示正常生育能力。

项目成果

Sekiguchi M, Tsuzuki T: "Oxidative nucleotide damage : consequences and prevention"Oncogene. 21(58). 8895-8904 (2002)

Sekiguchi M，Tsuzuki T：“氧化核苷酸损伤：后果和预防”癌基因。