中文摘要：

[目的]建立宫内p,p＇-DDE暴露跨代大鼠模型，观察雄性子代生殖毒性是否具有亲源性遗传特征及可能的表观遗传机制。[方法]SPF级的SD大鼠于孕8～15天给予每天每千克体重100mgp,p＇-DDE灌胃，另设溶剂对照组采用玉米油灌胃，孕鼠自由分娩，保留所有雄性仔鼠（F1代），同组别不同窝别的F1代仔鼠于出生后90天按雌雄比1：1交配，产生F2代仔鼠。染毒组和对照组雌雄F2代按以下分组设计两两交配后，产生F3代仔鼠，分组为：①雌雄均为对照组（C♂-C♀），②雌雄均为染毒组（DDE♂-DDE♀），③染毒组雄性与对照组雌性（DDE♂-C♀），④对照组雄性与染毒组雌性（C♂-DDE♀）。用计算机辅助精子分析系统（CASA）分析3代雄性仔鼠成年后的精子质量，亚硫酸氢钠基因组测序法检测堙露DMR2区域甲基化水平，实时荧光定量PCR分析印记基因表达。[结果]p,p＇-DDE可诱导F1、F2及F3代DDE♂-DDE♀、DDE♂-C♀精子数量和活力下降，F1代精子数量和活力分别从（70．63±11．79）×10^6／mL、（76．75土7．57）％下降至（50．00±13．08）×10^6／mL、（62．42±9．40）％；F2代精子数量和活力分别从（82．86±38．60）×10^6／mL、（82．14±6．44）％下降至（43．75±25．04）×10^6/mL、（60．88±25．03）％；F3代DDE♂-DDE♀精子数量及活力分别从（68．89±41．37）×10^6／mL、（68．56±10．67）％下降至（21．66±4．83）×10^6／mL和（29．33±32．70）％，F3代DDE♂-C♀精子数量和活力下降为（28．00±16．60）×10^6/mL和（34．60±31．60）％，差异均有统计学意义（均P〈0．05）。F1～F3代雄性仔鼠精子细胞Igf2DMR2区域（1、16、18位点）低甲基化，Igf2转录下调，H19转录上调，Igf2基因的转录水平和Igf2DMR2甲基化成正相关（r=-0．8065）。[结论]Igf2DMR2区域甲基化改变可能在p,p＇-DDE诱导的跨代雄性大鼠生殖毒性中起重要作?

英文摘要：

[Objective] To establish a transgenerational rat model with in utero p, p＇-DDE exposure and observe inherited characteristics and possible epigenetic mechanism. [ Methods ] Only the pregnant rats （FO） were administered with p, p＇-DDE （100 mg/kg per day according to body weight） or corn oil at the critical time of testis development （from gestation day 8 to 15）. Male rats （90 days old） of F1 generation were 1：1 mated with female of the same maternal treatment to produce F2 progeny. To reveal whether the male or female germ line was responsible for the transgenerational phenotype, F3 progeny was generated by intercrossing the control and treated male and female of F2 generation and divided as following groups： 1） control male plus control female （C ♂ -C♀）, 2） exposed male plus exposed female （DDE ♂ -DDE♀）, 3） exposed male plus control female （DDE ♂-C ♀）, and 4） control male plus exposed female （C ♂ -DDE ♀）. Sperm count and motility of male offspring of F1-F3 were analyzed with the Computer-Aided Sperm Analysis （CASA）. Igf2 DMR2 methylation was analyzed with bisulfite genomic sequencing. Gene expression was analyzed with real-time quantitative PCR. [ Results ] p, p＇-DDE decreased the sperm numbers and motility in F1 and F2 generations and DDE ♂-C♀ and DDE ♂-DDE♀ in F3 generation. In F1 generation, sperm numbers and motility decreased from （70.63 ± 11.79）× 10^6/mL and （75.75 ± 7.57）% to （70.63 ± 11.79） × 10^6/mL and （62.42 ± 9.40）% after p, p＇-DDE treatment, respectively. In F2 generation, sperm numbers and motility decreased from （82.86 ± 38.60） × 10^6/mL and （82.14 ± 6.44%）% to （43.75 ± 25.04） × 10^6/mL and （60.88 ± 25.03）% afterp, p＇-DDE treatment, respectively. As for DDE ♂ -C♀ in F3 generation, p, p＇-DDE decreased the sperm numbers and motility from （68.89 ± 41.37） × 10^6/mL and （68.56 ± 10.67）% to （21.66± 4.83） × 10^6/mL and （29.33 ± 32.70）%, respectively. As