Arachidonic acid metabolic pathway of the rabbit placenta

Abstract Placenta microsomes prepared from animals late in gestation (29 days) efficiently metabolize arachidonic acid into PGE 2 , PGF 2α , PGD 2 , PGD 2 , TxA 2 and little or no prostacyclin. In contrast to the late gestation placenta, the early (17 day) placental microsomes synthesize primarily PGE 2 . The cytosolic (100, 000 × g supernatant) fraction from early or late gestation placentae converted arachidonic acid, with a calcium dependent enzyme, into non-polar metabolites whose synthesis was inhibited by ETYA but not indomethacin. These metabolites were purified by HPLC and GC-MS analysis indicated the presence of 12-hydroxy-, 15-hydroxy-, and 11-hydroxy-eicosatetraenoic acid. The mitochondrial (8,000 × g pellet) produced PGE 2 ; PGF 2α ; 12-. 11-, 15-HETE; the C-17 fragment HHT; and the unusual cyclooxygenase metabolite 15-keto-PGE 2 . These biologically active metabolites may play a vital role in the reproductive function of the placenta.