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

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• 作者：Akihiro Arima ; Hirohito Kato ; Ryota Ise ; Yojiro Ooshima ; Ayumi Inoue ; Atsunobu Muneoka ; Shunichi Kamimura ; Toshio Fukusato ; Shunichiro Kubota ; Hiroshi Sumida ; Mineo Yasuda
• 关键词：TCDD ; Rhesus monkey ; Offspring ; Prostate ; Fibrosis ; Inflammatory response ; Microarray ; Prostatic dysfunction
• 刊名：Reproductive Toxicology
• 出版年：2010
• 出版时间：June 2010
• 年：2010
• 卷：29
• 期：3
• 页码：317-322
• 全文大小：879 K

文摘

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.