Embryonic prostaglandin H synthase‐2 (PHS‐2) expression and benzo[ α ]pyrene teratogenicity in PHS‐2 knockout mice 1

The developmental role of prostaglandin H synthase‐2 (PHS‐2), which converts xenobiotics such as benzo[ a ]pyrene (B[ a ]P) to toxic free radical intermediates, is poorly understood. In this study, we determined the embryonic expression and teratological relevance of PHS‐2 in pregnant CD‐1 and B6/129S7 PHS‐2 knockout mice. Wild‐type (+/+) B6/129S7 dams given B[ a ]P on gestational day (GD) 10 had three times more fetal malformations than did +/‐PHS‐2deficient dams ( P <0.05). GD 10–13 CD–1 embryos had high PHS–2 protein expression, and both + /+ and +/–GD 19 B6/129S7 fetuses had more B[ a ]P‐initiated malformations and postpartum lethality than did ‐/‐littermates ( P <0.05). Thus, embryonic PHS–2 is expressed constitutively during organogenesis and contributes substantially to B[ a ]P teratogenicity.—Parman, T., Wells, P. G. Embryonic prostaglandin H synthase‐2 (PHS‐2) expression and benzo[ a ]pyrene teratogenicity in PHS‐2 knockout mice. FASEB J. 16, 1001–1009 (2002)