Fetal baboons convert 18 : 3n-3 to 22 : 6n-3 in vivo: a stable isotope tracer study

Using [C-13]-tracers and direct fetal doses, we show for the first time tha t the fetal primate converts alpha -linolenic acid (18:3) to docosahexaenoi c acid (22:6) in vivo, and we estimate the relative bioefficacy of the two substrates for brain 22:6 accretion, Pregnant female baboons consumed a die t free of long chain polyunsaturates (LCP), with n-6/n-3 ratio of 10/1, In the third trimester of pregnancy (normal gestation = 182 days), they were i nstrumented with chronic indwelling catheters in the maternal femoral arter y and the fetal jugular artery. Doses of either [U-C-13]-18:3 (18:3*, n = 3 ) or [U-C-13]-22:6 (22:6*:, n = 2) were administered directly to the fetus. Blood was collected from fetus and mother, and the fetus tvas taken by ces arean section when electromyographic activity indicated that parturition wa s imminent. Fetal liver, brain, retina, and retinal pigment epithelium (RPE ) were collected, and C-13 fatty acids determined. In 18:3*-dosed animals, labeled n-3 LCP were detected in fetal plasma at 1 day post-dose and peaked at 2-3 days; brain 22:6* was constant at 3, 5, and 9 days post-dose, at 0. 57 +/- 0.03 percent of dose (%Dose), In 22:6*-dosed animals, brain 22:6* wa s similar at 3 and 9 days post-dose (4.64 +/- 0.43%Dose). From these data, we estimate that preformed 22:6 in the fetal bloodstream is 8-fold more eff icacious for brain 22:6 accretion than is 18:3, Retina 22:6* was stable at about 0.0008%Dose from 3 to 9 days in 18:3-dosed animals, but RPE 22:6* dro pped over the period; brain results were consistent with these observations . Liver showed about 0.5%Dose in 22:6* and in intermediary n-3 fatty acid m etabolites 20:5* and 22:5* at 3 days post-dose, and declined afterward, Bac k-transfer of labeled fatty acids to the maternal bloodstream was measurabl e but not sufficient to compromise the quantitative conversion data in fetu ses. We conclude 1) primate fetuses have the capacity to convert 18:3 to 22 :6 in vivo; 2) fetal brain 22:6* as %Dose plateaus by 3 days post-dose; 3) fetal plasma 22:6 is about 8-fold more effective as a substrate for brain 2 2:6 accretion compared with 18:3; and 4) the fetal liver is likely to be an important site of 18:3 to 22:6 conversion.