| First Author | Yoshioka W | Year | 2012 |
| Journal | Toxicol Sci | Volume | 127 |
| Issue | 2 | Pages | 547-54 |
| PubMed ID | 22430074 | Mgi Jnum | J:185740 |
| Mgi Id | MGI:5429803 | Doi | 10.1093/toxsci/kfs115 |
| Citation | Yoshioka W, et al. (2012) Critical role of microsomal prostaglandin E synthase-1 in the hydronephrosis caused by lactational exposure to dioxin in mice. Toxicol Sci 127(2):547-54 |
| abstractText | 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 mug 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. |
