δ-6-Desaturase (D6D) activity limits the desaturation of essential fatty acids (FA) during the synthesis of long chain polyunsaturated fatty acids (LC-PUFA). These LC-PUFA include vital n-6 and n-3 FA such as arachidonic acid (AA) and docosahexanoic acid (DHA). D6D is downregulated by glucocorticoids such as cortisol that are found at higher concentrations in the plasma and allantoic fluid of growth-retarded pig fetuses in late gestation (Ashworth et al. 2001). It is possible that some developmental problems of low birthweight neonates are caused by altered prenatal FA supply. In this study we investigated liver D6D gene expression and FA profile in growth-retarded and average-sized porcine fetuses at early, mid-and late gestation.
Large White X Landrace sows were exsanguinated under deep anaesthesia (8 % v/v halothane) on days 45 (n = 6), 65 (n = 6) and 100 (n = 6) of gestation in accordance with UK legislation. Day 65 and 100 fetuses were killed by an intracardiac injection of sodium pentobarbitone. RNA and lipid were extracted from the liver of an average sized (‘normal’) and the smallest (‘runt’) fetus from each litter. Gene expression of D6D was measured using Northern blot analysis and normalised to a maternal control. At day 100 D6D expression (2.96 ± 0.26) was significantly higher (P < 0.05, using ANOVA) than at days 45 (2.08 ± 0.14) and 65 (2.08 ± 0.19). Runt D6D expression was not significantly different from that of the normal at any stage of gestation. Fetal liver lipids were extracted, separated into phospho-neutral and glycolipid fractions and the FA profiles then determined by gas chromatography. Fetal size and stage of gestation had no significant effect on the proportion of FA as LC-PUFA in any lipid fraction.
In conclusion, D6D gene expression was increased at day 100 of gestation. This was not accompanied by greater proportion of FA as LC-PUFA and was, therefore, likely to be part of a general up-regulation of FA metabolism. No evidence for any downregulation of D6D gene expression was detected in runts. Furthermore, products of D6D (e.g. AA and DHA) were not found in reduced proportions in liver lipid. Therefore, the rate of desaturation by D6D was unlikely to have limited LC-PUFA supply in this model of intra-uterine growth retardation.
This work was funded by SEERAD.