Disruption of urine concentrating mechanism by dioxin induces hydronephrosis in mouse neonates

• YOSHIOKA Wataru

  Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan

• KAWAGUCHI Tatsuya

  Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan

• FUJISAWA Nozomi

  Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan

• AIDA-YASUOKA Keiko

  Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan

• TOHYAMA Chiharu

  Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan

抄録

2,3,7,8-Tetrachrolodibenzo-p-dioxin (TCDD) is a potent teratogen which induces hydronephrosis in the kidney of perinatal rodents. Because we previously found that the hydronephrosis in TCDD-exposed mouse neonates is not accompanied by ureteric physical obstruction that is known to be the major cause of hydronephrosis, we examined the ureteric peristalsis that is essential to transport urine from kidney to bladder, as well as the urine concentrating mechanism by the defect of which will result in overproduction of urine that will subsequently overwhelm handling capacity of the kidney. Dams of C57BL/6J mice were administered TCDD (0, 20, or 80 μg/kg) on postnatal day 1, and pups were subsequently exposed to TCDD via lactation. In TCDD-exposed pups, we did not observe alterations in frequency of peristaltic movement of ureter, but found an increased excretion in urine. When we administered antidiuretic drug, dDAVP (1 μg/kg/day), to TCDD-exposed pups to suppress urine production, this treatment significantly decreased the incidence and severity of TCDD-induced hydronephrosis, revealing that an increase in urine volume is the cause of TCDD-induced hydronephrosis. In addition, we observed a series of disrupting events in the prostaglandin synthesis pathway. That is, in TCDD-exposed pups, mRNA abundance of cPLA2α, cyclooxygenase-2, and microsomal prostaglandin E synthase-1, as well as urinary PGE₂ concentration were increased. In conclusion, TCDD exposure disrupts the urine concentrating mechanism, which results in the onset of hydronephrosis in mouse neonates. How the TCDD-induced upregulation of PGE₂ synthesis is involved in the pathogenesis warrant for a future study.

収録刊行物

• 日本毒性学会学術年会

  日本毒性学会学術年会 39.2 (0), AP-136-, 2012

  日本毒性学会

詳細情報

• CRID: 1390282680523847168
• NII論文ID: 130005009071
• DOI: 10.14869/toxpt.39.2.0.ap-136.0
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可