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.
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.
Arima
Akihiro
A
Drug Safety Research Laboratories, Shin Nippon Biomedical Laboratories Ltd., (SNBL), Kagoshima, Japan. arima-akihiro@snbl.co.jp
Kato
Hirohito
H
Ise
Ryota
R
Ooshima
Yojiro
Y
Inoue
Ayumi
A
Muneoka
Atsunobu
A
Kamimura
Shunichi
S
Fukusato
Toshio
T
Kubota
Shunichiro
S
Sumida
Hiroshi
H
Yasuda
Mineo
M
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
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; C038902:1,4-dioxin