title: 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.
abstract: 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.
authors.affiliation: School of Biology, University of Nottingham, University Park, Nottingham NG7 2RD, UK. david.bell@nottingham.ac.uk
authors.forename: David R
authors.initials: DR
authors.lastname: Bell
authors.forename: Sally
authors.initials: S
authors.lastname: Clode
authors.forename: Ming Qi
authors.initials: MQ
authors.lastname: Fan
authors.forename: Alwyn
authors.initials: A
authors.lastname: Fernandes
authors.forename: Paul M D
authors.initials: PM
authors.lastname: Foster
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: George
authors.initials: G
authors.lastname: Loizou
authors.forename: Alan
authors.initials: A
authors.lastname: MacNicoll
authors.forename: Brian G
authors.initials: BG
authors.lastname: Miller
authors.forename: Martin
authors.initials: M
authors.lastname: Rose
authors.forename: Lang
authors.initials: L
authors.lastname: Tran
authors.forename: Shaun
authors.initials: S
authors.lastname: White
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D004822:Epididymis / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005298:Fertility / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D009043:Motor Activity / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010502:Perineum / Q000254:growth & development; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012741:Sexual Maturation / Q000187:drug effects; D013076:Sperm Count; D013094:Spermatozoa / Q000187:drug effects* / Q000473:pathology; D013737:Testis / Q000187:drug effects / Q000473:pathology; D023382:Toxicity Tests, Acute
chemical_list: D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins