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新生儿暴露于环境污染物对大鼠睾丸DNA甲基化的影响

[Effect of neonatal exposure to environmental pollutants on the DNA methylation of rat testis].

作者信息

Li Ke-Yong, Xiao Wu-Sheng, Wu Qing, Chang Xiu-Li, Zhou Zhi-Jun, Zhang Jie, Su De-Qi

机构信息

Department of Occupational Health, School of Public Health of Fudan University, Shanghai 200032, China.

出版信息

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2009 Nov;27(11):649-54.

PMID:20137407
Abstract

OBJECTIVE

To investigate the effects of neonatal exposure of DNA methylation inhibitor, Cadmium and PCB153 on DNA methylation, apoptosis and spermatogenesis in SD rats.

METHODS

Neonatal SD rats were randomly divided into 10 groups and received oral administrations of PCB153 (0.025, 0. 250, 2.500 mg/kg), or Cadmium (1, 2, 4 mg/kg), or positive control 5-Aza-CdR (0.025, 0.250 mg/kg), or vehicle control for five days from PND3. Half of the rats were killed 24 h after the last administration. The remains were fed until 12 weeks. Sperm numbers, apoptosis and DNA methylation levels in testis were investigated.

RESULTS

The daily sperm production was significantly decreased in each neonatal exposed group (P < 0.05). Neonatal rats exposed to 5-Aza-CdR and Cadmium reduced the global DNA methylation level, increased apoptosis, while PCB153 exposure did not significantly change DNA methylation and apoptosis.

CONCLUSION

Neonatal rats exposed to chemicals could reduce spermatogenesis via multiple pathways. Lower DNA methylation and increased neonatal apoptosis were suggested as one of the causes.

摘要

目的

研究新生期暴露于DNA甲基化抑制剂、镉和多氯联苯153对SD大鼠DNA甲基化、细胞凋亡及精子发生的影响。

方法

将新生期SD大鼠随机分为10组,从出生后第3天起连续5天分别经口给予多氯联苯153(0.025、0.250、2.500 mg/kg)、镉(1、2、4 mg/kg)、阳性对照5-氮杂-2'-脱氧胞苷(0.025、0.250 mg/kg)或溶剂对照。末次给药后24小时处死一半大鼠,其余大鼠饲养至12周龄。检测睾丸中的精子数量、细胞凋亡及DNA甲基化水平。

结果

各新生期暴露组的每日精子生成量均显著降低(P<0.05)。新生期暴露于5-氮杂-2'-脱氧胞苷和镉的大鼠,其整体DNA甲基化水平降低,细胞凋亡增加,而暴露于多氯联苯153的大鼠,其DNA甲基化和细胞凋亡无明显变化。

结论

新生期暴露于化学物质可通过多种途径降低精子发生。DNA甲基化水平降低及新生期细胞凋亡增加被认为是其原因之一。

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