Address correspondence to: William L. Smith, 513 Biochemistry Building, Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824, USA. Phone:(517) 355-1604; Fax:(517) 353-9334; E-mail: smithww@ msu. edu. lation, PGHS-2 deficiency also impedes blastocyst implantation and decidualization. PGI2 has been demonstrated to be the prostanoid involved in this process, and it is also formed through PGHS-2 (Table 1)(12). Interestingly, although prostanoids appear to act primarily via G protein–linked receptors (5), the nuclear peroxisomal proliferator–activated receptor PPARδ appears to mediate the action of PGI2 in implantation (12), suggesting that alternative routes may exist by which PGI2 can influence gene expression. Neonatal development. Although it is widely believed that PGHS-1 acts in development, there are few reports available to support this claim, and recent studies suggest that PGHS-2 plays a more important role, at least in neonatal development (13, 14). PGHS-2–deficient mice develop a severe renal pathology that is not mimicked by administration of NSAIDs to adult mice (2, 3). Initially, some investigators believed that this phenotype represented a compensatory artifact of the PGHS-2 knockout, but Komhoff et al.(13) showed recently that postnatal treatment with a PGHS-2–selective NSAID caused a severe reduction in glomerular diameter in the neonatal mouse kidney. This was the same renal pathology as seen in PGHS-2–null mice (13) and could not be caused by treating adult mice with the PGHS-2–selective inhibitor. Another neonatal event in the mouse in which PGHS-2 has a key role is in the closure of the ductus arteriosus (14). Although the ductus closes normally in PGHS-1–null mice, about 35% of PGHS-2–null mice die with a patent ductus within 48 hours of birth. In wild-type mice, PGHS-2, but not PGHS-1, is seen by immunohistochemistry to be significantly induced in the smooth muscle cells of the ductus during closure; however, the fact that 65% of COX-2–null mice survived to weaning suggests that PGHS-1 can play a compensatory role. Indeed, a reduction in PGHS-1 gene dosage from wild-type to hetrozygosity further increases the incidence of patent ductus arteriosus and decreases the 48-hour survival of PGHS-2–null mice to about 20%. Because a role for PGHS-1 is only evident when PGHS-2 is absent, it is unlikely that PGHS-1 is involved in ductus closure in wild-type mice. These examples indicate that PGHS-2 has key roles during postpartum development. Because the birthing process involves a number of physiological changes and stresses that could induce PGHS-2, and because PGHS-2–null mice have decreased survival at all ages, it may be useful to search for other neonatal tissues in which PGHS-2 induction promotes normal neonatal development.