论文部分内容阅读
[目的]探讨暴露于DNA甲基化抑制剂5-Aza-2’-deoxycytidine(5-Aza-CdR)对新生SD大鼠生长发育和成年精子发生的影响。[方法]新生大鼠随机分为3组,每组24只雄鼠。自出生第3天(postnatal day 3,PND 3)开始经口给予5-Aza-CdR 25、250μg/kg,对照组给予等量的溶剂。连续暴露5d,最后一次暴露结束后24h,处死半数雄鼠(幼鼠)。剩余部分继续喂养至12周龄(成鼠),乙醚麻醉。取睾丸组织做病理学检查、精子头计数等,附睾做精子畸形检查。[结果]随着剂量的增加,幼鼠体重出现下降趋势,与对照组比较差异有统计学意义(P<0.05)。组织病理学发现幼鼠睾丸组织中出现空泡变性。检查发现染毒结束后继续喂养至12周的成鼠睾丸组织无明显形态和组织学变化;但每克睾丸组织精子头计数及每日精子生成量随幼年时暴露剂量增加呈现下降趋势(P<0.05),而精子畸形率随剂量增加呈现上升趋势(P<0.05)。[结论]新生大鼠对DNA甲基化抑制制5-Aza-CdR生殖毒性作用敏感,低剂量短时间的暴露即可引起成年期生殖功能的异常。
[Objective] To investigate the effects of exposure to 5-Aza-2’-deoxycytidine (5-Aza-CdR), a DNA methylation inhibitor, on the growth and development of adult SD rats and adult spermatogenesis. [Methods] Newborn rats were randomly divided into three groups of 24 male rats. 5-Aza-CdR 25,250 μg / kg was administered orally from postnatal day 3 (PND 3), and the control group was given the same amount of solvent. After 5 days of continuous exposure, half of the male rats (young rats) were killed 24 hours after the last exposure. The remaining part of the feed to 12 weeks of age (into rats), ether anesthesia. Take testicular tissue pathology, sperm head count, epididymis sperm deformity check. [Result] With the increase of dose, the body weight of juvenile rats showed a downward trend, which was significantly different from the control group (P <0.05). Histopathology revealed vacuolar degeneration in the testes of young rats. The results showed that there was no obvious morphological and histological changes in the testis tissue of adult rats that were fed to the 12th week after exposure. However, the number of spermatozoa and daily sperm production per gram of testis showed a decreasing trend with the increase of exposure dose (P < 0.05), while the sperm deformity rate increased with dose (P <0.05). [Conclusion] Neonatal rats are sensitive to 5-Aza-CdR reproductive toxicity induced by DNA methylation. Exposure to low doses and short-term exposure can cause reproductive abnormalities in adulthood.