title: Critical role of microsomal prostaglandin E synthase-1 in the hydronephrosis caused by lactational exposure to dioxin in mice.
abstract: 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. PGE(2), 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 PGE(2) synthase, in TCDD-induced hydronephrosis. A dose of 10 μg TCDD/kg to dams increased mPGES-1 messenger RNA abundance, urinary PGE(2) 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 PGE(2) 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.
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Yoshioka
authors.forename: Keiko
authors.initials: K
authors.lastname: Aida-Yasuoka
authors.forename: Nozomi
authors.initials: N
authors.lastname: Fujisawa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Seiichiroh
authors.initials: S
authors.lastname: Ohsako
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Hara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uematsu
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tohyama
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015232:Dinoprostone / Q000652:urine; D005260:Female; D006869:Hydronephrosis / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D019746:Intramolecular Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007774:Lactation; D018811:Maternal Exposure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone