(A) A selected ion-monitoring trace of the methoxime derivative of endogenous PGEM (9,15-dioxo-11α-hydroxy-2,3,4,5-tetranor-prostane-1,20-dioic-17,17,18,18,19,19-d6 acid) (bottom panel) and its hexadeuterated internal standard (top panel). (B) Urinary PGEM decreased significantly in both male and female PGHS-2 KO or PGHS-2Y385F mice compared with WT controls on a mixed C57BL/6 × 129/Sv genetic background (n = 5–6; *P < 0.05; **P < 0.001). PGEM was also significantly lower in PGHS-1 KD and PGHS-1 KO groups compared with WT mice of mixed C57BL/6 × 129/Sv genetic background (n = 5–6; *P < 0.05; **P < 0.001). PGEM was significantly higher in PGHS-2Y385F mice compared with PGHS-2 KO mice (#P < 0.05) on the same genetic background.