title: In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces disruption of glands of the prostate and fibrosis in rhesus monkeys.
abstract: We investigated the effects that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure has on the prostate in rhesus monkey offspring. Dams received 0, 30 or 300 ng/kg TCDD subcutaneously on Day 20 of gestation, and then 5% of the initial dose was injected every 30 days until Day 90 after delivery. The offspring were maintained until reaching sexual maturity, and examined histopathologically. Dose-dependent decreases in glands of the prostate and widespread fibrosis were observed in offspring. It is noteworthy that 7 years from the final lactational TCDD exposure, inflammatory cell infiltration and disruption of glands of the prostate were still observed. Differential mRNA expression associated with fibrosis, inflammatory response and disruption of cell components were demonstrated by microarray analysis, with up-regulation of TGM4, TGFB1, COL1A1 and MMP2 confirmed. In conclusion, in utero and lactational exposure to TCDD induced dose-related prostatic fibrosis, indicating prostatic dysfunction and inducible semen quality reduction in second-generation rhesus monkeys.
authors.affiliation: Drug Safety Research Laboratories, Shin Nippon Biomedical Laboratories Ltd., (SNBL), Kagoshima, Japan. arima-akihiro@snbl.co.jp
authors.forename: Akihiro
authors.initials: A
authors.lastname: Arima
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kato
authors.forename: Ryota
authors.initials: R
authors.lastname: Ise
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Ooshima
authors.forename: Ayumi
authors.initials: A
authors.lastname: Inoue
authors.forename: Atsunobu
authors.initials: A
authors.lastname: Muneoka
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kamimura
authors.forename: Toshio
authors.initials: T
authors.lastname: Fukusato
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Kubota
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sumida
authors.forename: Mineo
authors.initials: M
authors.lastname: Yasuda
mesh_terms: D000818:Animals; D004147:Dioxins; D004305:Dose-Response Relationship, Drug; D005260:Female; D005355:Fibrosis / Q000378:metabolism; D007774:Lactation / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D009141:Musculoskeletal System / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D011247:Pregnancy; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism; D055101:Semen Analysis; D015854:Up-Regulation
chemical_list: D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; C038902:1,4-dioxin