Prostaglandin E2 is only slightly metabolized in the fetal circulation of perfused human placenta

The metabolism of prostaglandin E2 (PGE2) was investigated in the fetal circulation of one cotyledon or a group of cotyledons in human term placentas by in vitro perfusion technique. When 100 nmol of 14C-PGE2 was infused in 2.5 minutes into the chorionic artery, 75 +/- 5% (mean +/- SEM, n=8) of the infused radioactivity appeared in the nonrecirculating venous effluent in six minutes. Most of the radioactivity was in the fraction of unmetabolized PGE2, only 6-13% of the radioactivity in the effluent appeared in metabolite fraction, the major metabolite being 14-keto-13,14-dihydro-PGE2. The amount of metabolites in 0-6 min effluent was 0.13 +/- 0.01 nmol/g of perfused placenta. This rate of formation of PGE2 metabolites is very low compared to the activity of NAD+-dependent 15-hydroxyprostaglandin dehydrogenase, which was 183 +/- 19 nmol x min-1 x g of tissue-1 (n=5) when measured from the 100.000 g supernatant fraction of homogenized human placenta using 14C-PGE2 as the substrate. The present study indicates that PGE2 is only slightly metabolized in the fetal circulation of human placenta, in spite of high activity of 15-hydroxyprostaglandin dehydrogenase in placental tissue.