Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan, People's Republic of China.
Hum Exp Toxicol. 2014 Apr;33(4):424-34. doi: 10.1177/0960327112474849. Epub 2013 Jun 5.
Carbon disulfide (CS2) has reproductive toxicity but the mechanism remains unclear. The aim of the present study was to investigate the effect of oxidative stress and DNA damage on embryo implantation of mice exposed to CS2 at peri-implantation. CS2 exposure was on gestational day 3 (GD3), GD4, GD5 and GD6, separately, and the number of embryonic day 9 (E9) mouse embryos was obtained. DNA damage of endometrial cells, oxidative stress and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) level in uterus tissues were tested with time series at different end points after exposure. The number of E9 mouse embryos significantly decreased in all CS2 exposure groups, especially on GD4 exposure. The rates of embryo implantation decreased by 43.05%, 63.74%, 60.45% and 47.26% for CS2 exposure on GD3, GD4, GD5 and GD6, respectively. Oxidative stress significantly increased within 24 h and reached the top level at 18 h after exposure. The same time-dependent trend was observed no matter when the exposure happened at peri-implantation. 8-OH-dG significantly increased at 18 h and 24 h after exposure by 893.8% and 647.4%, respectively, when compared with the control. The indexes of DNA damage significantly increased at 6 h after exposure, which appeared earlier than the changes of oxidative stress and 8-OH-dG. Besides, both oxidative stress and DNA damage showed a strong negative correlation with the number of E9 mouse embryos. The present study illustrated that CS2 directly induced DNA damage in endometrial cells and enhanced the action through oxidative stress, both of which were responsible for CS2-induced embryo loss.
二硫化碳（CS2）具有生殖毒性，但作用机制尚不清楚。本研究旨在探讨 CS2 对着床期小鼠胚胎植入的氧化应激和 DNA 损伤的影响。CS2 暴露分别在妊娠第 3 天（GD3）、第 4 天（GD4）、第 5 天（GD5）和第 6 天（GD6）进行，获得胚胎第 9 天（E9）的小鼠胚胎数量。通过时间序列检测不同暴露终点后子宫内膜细胞的 DNA 损伤、氧化应激和子宫组织中的 8-羟基-2'-脱氧鸟苷（8-OH-dG）水平。所有 CS2 暴露组的 E9 小鼠胚胎数量均显著减少，尤其是在 GD4 暴露组。CS2 暴露于 GD3、GD4、GD5 和 GD6 时，胚胎植入率分别下降了 43.05%、63.74%、60.45%和 47.26%。氧化应激在暴露后 24 小时内显著增加，并在 18 小时达到高峰。无论在着床期何时暴露，都观察到了相同的时间依赖性趋势。8-OH-dG 在暴露后 18 小时和 24 小时分别增加了 893.8%和 647.4%，与对照组相比显著增加。DNA 损伤指标在暴露后 6 小时明显增加，早于氧化应激和 8-OH-dG 的变化。此外，氧化应激和 DNA 损伤均与 E9 小鼠胚胎数量呈强烈负相关。本研究表明，CS2 直接诱导子宫内膜细胞的 DNA 损伤，并通过氧化应激增强其作用，这两者均导致 CS2 引起的胚胎丢失。
