PMID- 17545212 OWN - NLM STAT- MEDLINE DCOM- 20071004 LR - 20161124 IS - 1096-6080 (Print) IS - 1096-0929 (Linking) VI - 99 IP - 1 DP - 2007 Sep TI - Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the developing male Wistar(Han) rat. I: No decrease in epididymal sperm count after a single acute dose. PG - 214-23 AB - It has been reported that fetal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes defects in the male reproductive system of the rat. We set out to replicate and extend these effects using a robust experimental design. Groups of 75 (control vehicle) or 55 (50, 200, or 1000 ng of TCDD/kg bodyweight) female Wistar(Han) rats were exposed to TCDD on gestational day (GD)15, then allowed to litter. The high-dose group dams showed no sustained weight loss compared to control, but four animals had total litter loss. Pups in the high-dose group showed reduced body weight up till day 21, and pups in the medium dose group showed reduced body weight in the first week postpartum. Balano-preputial separation was significantly delayed in the high-dose group male offspring. There were no significant effects of treatment when the offspring were subjected to a functional observational battery or mated with females to assess reproductive capability. Twenty-five males per group were killed on postnatal day (PND) 70, and approximately 60 animals per group (approximately 30 for the high-dose group) on PND120 to assess seminology and other end points. At PND120, the two highest dose groups showed a statistically significant elevation of sperm counts, compared to control; however, this effect was small (approximately 30%), within the normal range of sperm counts for this strain of rat, was not reflected in testicular spermatid counts nor PND70 data, and is therefore postulated to have no biological significance. Although there was an increase in the proportion of abnormal sperm at PND70, seminology parameters were otherwise unremarkable. Testis weights in the high-dose group were slightly decreased at PND70 and 120, and at PND120, brain weights were decreased in the high-dose group, liver to body weight ratios were increased for all three dose groups, with an increase in inflammatory cell foci in the epididymis in the high-dose group. These data show that TCDD is a potent developmental toxin after exposure of the developing fetus but that acute developmental exposure to TCDD on GD15 caused no decrease in sperm counts. FAU - Bell, David R AU - Bell DR AD - School of Biology, University of Nottingham, University Park, Nottingham NG7 2RD, UK. david.bell@nottingham.ac.uk FAU - Clode, Sally AU - Clode S FAU - Fan, Ming Qi AU - Fan MQ FAU - Fernandes, Alwyn AU - Fernandes A FAU - Foster, Paul M D AU - Foster PM FAU - Jiang, Tao AU - Jiang T FAU - Loizou, George AU - Loizou G FAU - MacNicoll, Alan AU - MacNicoll A FAU - Miller, Brian G AU - Miller BG FAU - Rose, Martin AU - Rose M FAU - Tran, Lang AU - Tran L FAU - White, Shaun AU - White S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070601 PL - United States TA - Toxicol Sci JT - Toxicological sciences : an official journal of the Society of Toxicology JID - 9805461 RN - 0 (Environmental Pollutants) RN - 0 (Polychlorinated Dibenzodioxins) SB - IM MH - Administration, Oral MH - Animals MH - Animals, Newborn MH - Behavior, Animal/drug effects MH - Body Weight/drug effects MH - Dose-Response Relationship, Drug MH - Environmental Pollutants/*toxicity MH - Epididymis/*drug effects/pathology MH - Female MH - Fertility/drug effects MH - Male MH - Maternal Exposure/*adverse effects MH - Motor Activity/drug effects MH - Organ Size/drug effects MH - Perineum/growth & development MH - Polychlorinated Dibenzodioxins/*toxicity MH - Pregnancy MH - Rats MH - Rats, Wistar MH - Sexual Maturation/drug effects MH - Sperm Count MH - Spermatozoa/*drug effects/pathology MH - Testis/drug effects/pathology MH - *Toxicity Tests, Acute EDAT- 2007/06/05 09:00 MHDA- 2007/10/05 09:00 CRDT- 2007/06/05 09:00 PHST- 2007/06/05 09:00 [pubmed] PHST- 2007/10/05 09:00 [medline] PHST- 2007/06/05 09:00 [entrez] AID - kfm140 [pii] AID - 10.1093/toxsci/kfm140 [doi] PST - ppublish SO - Toxicol Sci. 2007 Sep;99(1):214-23. doi: 10.1093/toxsci/kfm140. Epub 2007 Jun 1.