PMID- 30153481 OWN - NLM STAT- MEDLINE DCOM- 20180924 LR - 20180924 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 297 DP - 2018 Nov TI - Transgenerational impaired spermatogenesis with sperm H19 and Gtl2 hypomethylation induced by the endocrine disruptor p,p'-DDE. PG - 34-41 LID - S0378-4274(18)31813-7 [pii] LID - 10.1016/j.toxlet.2018.08.015 [doi] AB - The hypothesis of fetal origins unraveled that environmental exposures in early life could alter epigenetic modifications in the male germ-line, increasing the susceptibility to adult-onset diseases for generations. In our previous study, p,p'-dichlorodiphenoxydichloroethylene (p,p'-DDE), a representative endocrine disruptor, was found to induce transgenerational impaired male fertility with sperm Igf2 hypomethylation. However, whether other imprinted genes involved remains uncovered. In the present study, we administered p,p'-DDE (100 mg/kg body weight) to pregnant Sprague-Dawley rats from gestational day (GD) 8 to GD15. Male F1 offspring were mated with the females from the same group to obtain F2 progeny. F3 progeny was obtained by inter-crossing the control and exposed F2 generation. Gestational exposure to p,p'-DDE impaired the testis histology and decreased the sperm fertility with H19 and Gtl2 hypomethylation in F1 offspring. Interestingly, this impaired spermatogenesis and DNA hypomethylation were maintained through F2 and F3 generations. DNA methyltransferase DNMT1 and 3a were significantly decreased in the embryonic testis of p,p'-DDE-treated F1 and F2 generation and returned to control levels by the F3 generation. p,p'-DDE induced a transgenerational impaired spermatogenesis with altered epigenetic modification, posing significant implications for disease etiology. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Song, Yang AU - Song Y AD - Medical college, Hangzhou Normal University, No. 16 Xuelin Road, Xiasha Higher Education Park, Hangzhou 310036, Zhejiang, PR China. Electronic address: sygp_0@163.com. FAU - Yang, Lei AU - Yang L AD - Medical college, Hangzhou Normal University, No. 16 Xuelin Road, Xiasha Higher Education Park, Hangzhou 310036, Zhejiang, PR China. Electronic address: yanglei62@hznu.edu.cn. LA - eng PT - Journal Article DEP - 20180825 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Endocrine Disruptors) RN - 0 (H19 long non-coding RNA) RN - 0 (Insecticides) RN - 0 (MEG3 non-coding RNA, rat) RN - 0 (RNA, Long Noncoding) RN - 4M7FS82U08 (Dichlorodiphenyl Dichloroethylene) SB - IM MH - Animals MH - DNA Methylation/drug effects MH - Dichlorodiphenyl Dichloroethylene/*toxicity MH - Endocrine Disruptors/*toxicity MH - Epigenesis, Genetic/drug effects MH - Female MH - Infertility, Male/chemically induced/genetics MH - Insecticides/*toxicity MH - Male MH - Pregnancy MH - Prenatal Exposure Delayed Effects MH - RNA, Long Noncoding/*drug effects/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Sperm Count MH - Spermatogenesis/*drug effects MH - Testis/pathology OTO - NOTNLM OT - DNA methylation OT - Imprinted genes OT - Spermatogenesis OT - Transgeneration OT - p,p'-DDE EDAT- 2018/08/29 06:00 MHDA- 2018/09/25 06:00 CRDT- 2018/08/29 06:00 PHST- 2018/03/30 00:00 [received] PHST- 2018/06/12 00:00 [revised] PHST- 2018/08/24 00:00 [accepted] PHST- 2018/08/29 06:00 [pubmed] PHST- 2018/09/25 06:00 [medline] PHST- 2018/08/29 06:00 [entrez] AID - S0378-4274(18)31813-7 [pii] AID - 10.1016/j.toxlet.2018.08.015 [doi] PST - ppublish SO - Toxicol Lett. 2018 Nov;297:34-41. doi: 10.1016/j.toxlet.2018.08.015. Epub 2018 Aug 25.