Journal Article

Critical Role of Microsomal Prostaglandin E Synthase-1 in the Hydronephrosis Caused by Lactational Exposure to Dioxin in Mice

Wataru Yoshioka, Keiko Aida-Yasuoka, Nozomi Fujisawa, Tatsuya Kawaguchi, Seiichiroh Ohsako, Shuntaro Hara, Satoshi Uematsu, Shizuo Akira and Chiharu Tohyama

in Toxicological Sciences

Volume 127, issue 2, pages 547-554
Published in print June 2012 | ISSN: 1096-6080
Published online March 2012 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfs115
Critical Role of Microsomal Prostaglandin E Synthase-1 in the Hydronephrosis Caused by Lactational Exposure to Dioxin in Mice

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Hydronephrosis induced in the kidney of neonatal mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) via lactation is a sensitive and characteristic hallmark of TCDD teratogenicity. We previously found that cyclooxygenase-2 (COX-2) activity induced in mouse neonate kidneys by lactational TCDD exposure is required for this toxicity. COX-2 is an inducible form of cyclooxygenase and is responsible for producing prostaglandins (PGs) and thromboxane. PGE2, a prostaglandin, is elevated in TCDD-exposed mouse pups. In this study, we investigated the role of microsomal prostaglandin E synthase-1 (mPGES-1), an inducible form of PGE2 synthase, in TCDD-induced hydronephrosis. A dose of 10 μg TCDD/kg to dams increased mPGES-1 messenger RNA abundance, urinary PGE2 levels, and the incidence of hydronephrosis in mPGES-1 wild-type pups. In homozygous mPGES-1 knockout (KO) mice, in contrast, TCDD-induced hydronephrosis was suppressed, demonstrating an essential role of mPGES-1 in the response. Lack of the mPGES-1 gene also suppressed urinary PGE2 level to near the basal level in TCDD-exposed pups. In conclusion, mPGES-1 upregulation upon lactational TCDD exposure is a causal factor for TCDD-induced hydronephrosis in mouse neonates.

Keywords: dioxin; kidney; developmental toxicity

Journal Article.  4719 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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