title: A dose-response analysis of the reproductive effects of a single gestational dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin in male Long Evans Hooded rat offspring.
abstract: Male rats exposed in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) display reduced fertility as a consequence of the direct action of TCDD on the epididymides, as well as delayed puberty and altered reproductive organ weights. The current study provides dose-response data for the reproductive effects of TCDD, administered during pregnancy, with an emphasis on the effects of TCDD on testicular, epididymal, and ejaculated sperm numbers. Long Evans Hooded rats were dosed by gavage with 0, 0.05, 0.20, or 0.80 microg TCDD/kg on Day 15 of gestation. After birth, growth, viability, and developmental landmarks were monitored in both male and female offspring. Shortly after puberty (49 and 63 days of age) and at 15 months of age, male offspring were necropsied. Growth and viability of the pups were reduced only at 0.80 microg TCDD/kg, eye opening was accelerated (all dosage groups), and puberty was delayed (at 0.20 and 0.80 microg TCDD/kg). Treated progeny displayed transient reductions in ventral prostate and seminal vesicle weights, while epididymal sperm reserves and glans penis size were permanently reduced. Ejaculated sperm numbers were reduced (45% in the 0.8 and by 25% in the 0.05 and 0.2 microg TCDD/kg dosage groups) to a greater degree than were cauda or caput/corpus epididymal or testicular (unaffected) sperm numbers. In conclusion, administration of TCDD on Day 15 of pregnancy at 0.05 microg/kg altered eye opening and reduced ejaculated sperm counts, while higher dosage levels also delayed puberty and permanently reduced cauda epididymal sperm reserves.
authors.affiliation: Reproductive Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
authors.forename: L E
authors.initials: LE
authors.lastname: Gray
authors.forename: J S
authors.initials: JS
authors.lastname: Ostby
authors.forename: W R
authors.initials: WR
authors.lastname: Kelce
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects*; D005837:Genitalia, Male / Q000187:drug effects*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D013076:Sperm Count / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013739:Testosterone / Q000097:blood
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D013739:Testosterone