Study of DNA methylation and gene expression during development of male reproductive organs. -Global analysis of DNA methylation using Restriction Landmark Genomic Scanning (RLGS) method-

男性生殖器官发育过程中DNA甲基化和基因表达的研究。

• 批准号: 14370004
• 负责人: MORI Chisato
• 金额: $ 8.9万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370004/
• 关键词: reproductive organ; development; DNA methylation; RLGS method; gene expression; endocrine disruptor; diethylstilbestrol; epigenetics; DNAメチレーション

Neonatal C57BL/6 mice were exposed to 3 μg/pup/day of synthetic estrogen, diethylstilbestrol(DBS). At day 30, epididymidis (from male mice) and uteri (from female mice) were teken, and their status of DNA methylation were analyzed using restriction landmark genomic scanning method (RLGS). In epididymis and uterus, the methylation of 7 and 11 loci (out of about 1000 loci) were changed, respectively. Then lower dose of DBS (0.3、0.03、0.003 μg/pup/day) were examined, and clear dose dependency of the methylation change was observed.We analyzed the loci those methylation were changed by DBS. Four loci from epididymis and 3 loci from uterus were cloned, and the characteristics of them such as GC content, chromosomal distribution, neighbor genes were examined. Four loci from epididymis were near from zinc finger protein, RNA helicase, protein kinase associated gene, retinal disease associated gene, respectively. Three loci from uterus were not close to known genes.The mechanism by which methylation was changed, and the effect of that change on development of male reproductive organs remained to be elucidated.

新生C57BL/6小鼠ig合成雌激素己烯雌酚（DBS） 3 μg/ d。第30天，检测雄性小鼠的附睾和雌性小鼠的子宫，采用限制性内切标记基因组扫描法（RLGS）分析其DNA甲基化状态。在大约1000个位点中，附睾和子宫分别有7个和11个位点的甲基化发生了改变。然后观察低剂量DBS（0.3、0.03、0.003 μg/pup/d）对甲基化变化的影响。我们分析了那些甲基化被DBS改变的位点。从附睾和子宫分别克隆了4个基因座和3个基因座，并对其GC含量、染色体分布、邻近基因等特征进行了检测。附睾中锌指蛋白、RNA解旋酶、蛋白激酶相关基因、视网膜疾病相关基因有4个位点。来自子宫的三个位点与已知基因不接近。甲基化改变的机制以及这种改变对男性生殖器官发育的影响仍有待阐明。

项目成果

Pilot study to reduce dioxins in the human body.

减少人体内二恶英的试点研究。

• 发表时间: 2004
• 期刊: Internal Medicine Vol.43,No.9
• 作者: Sakurai K;Todaka E;Saito Y;Mori C
• 通讯作者: Mori C

Effect of neonatal exposure to diethylstilbestrol on testicular gene expression in adult mouse : comprehensive analysis with cDNA subt-raction method.

新生儿接触己烯雌酚对成年小鼠睾丸基因表达的影响：cDNA 扣除法综合分析。

• 发表时间: 2004
• 期刊: International Journal of Andrology 27
• 作者: Matsuno;Yoshiharu
• 通讯作者: Yoshiharu

Nakagawa, Soichi: "Detection of mitomycin C-induced testicular toxicity by micronucleus assay in mice."Reprod Med Biol. 2・2. 69-72 (2003)

Nakakawa，Soichi：“通过小鼠微核测定检测丝裂霉素 C 诱导的睾丸毒性。”Reprod Med Biol 2·2 (2003)。

森 千里: "ヒト胎児の複合曝露に対する新しい影響評価法の開発-トキシコゲノミクヌを用いて"医学のあゆみ. 204. 954-958 (2003)

Chisato Mori：“开发一种评估多次暴露对人类胎儿影响的新方法 - 使用毒理学”《医学史》204. 954-958 (2003)。

Flutamide induces ultrastructural changes in spermatids and the ectoplasmic specialization between the Sertoli cell and spermatids in mouse testes

• DOI: 10.1016/j.reprotox.2004.02.011
• 发表时间: 2004-06-01
• 期刊: REPRODUCTIVE TOXICOLOGY
• 影响因子: 3.3
• 作者: Anahara, R;Toyama, Y;Mori, C
• 通讯作者: Mori, C