ARACHIDONATE METABOLISM IN HUMAN PLACENTA, FETAL MEMBRANES, DECIDUA AND MYOMETRIUM - LIPOXYGENASE AND CYTOCHROME-P450 METABOLITES AS MAIN PRODUCTS IN HPLC PROFILES

Eicosanoids play a key role in pregnancy maintenance and parturition. We investigated the metabolism of arachidonic acid (AA) in short-term tissue cultures of placenta, fetal membranes, decidua and myometrium. Tissues were obtained from caesarean sections before the onset of labo ur after uncomplicated pregnancies. The released metabolites were anal ysed by high performance liquid chromatography (HPLC) and specific imm unoassays. In radiotracer experiments tissues were labelled with [H-3] -AA and metabolites released after incubation with calcium ionophore A (23187) were profiled by HPLC. Decidua was more active in metabolizing AA (turnover 34 per cent) than myometrium (28 per cent), placenta (21 per cent) and fetal membranes (17 per cent). Main product in placenta , decidua and myometrium was 12-hydroxyeicosatetraeinoic (12-HETE) (de cidua: 19 per cent of released radioactivity, myometrium 14 per cent, placenta 7 per cent). Fetal membranes formed 5-HETE as main product. A nother major metabolite in placenta, fetal membranes and decidua was c haracterized by HPLC as 5(6)-epoxyeicosatrienoic acid. Only myometrium released appreciable amounts of prostaglandins in form of 6-keto-pros taglandin F-1 alpha. In non-radioactive experiments formation of eicos anoids from endogenous AA was investigated by HPLC (fluorescence- and UV-detection) and immunoassays. These experiments confirmed the high p roduction of 12-HETE and the low formation of prostaglandins. Our resu lts suggest that the biological role of AA-metabolites, other than pro staglandins, have as pet been underestimated. (C) 1996 W. B. Saunders Company Ltd