| Summary: | Diabetes is associated with abnormal nutrient metabolism particularly carbohydrates and lipids. In pregnancy, this diabetes-associated metabolic perturbation has been shown to alter, qualitatively and quantitatively. the uterine lipid environment and consequently the fatty acids delivered to the developing foetus. Perhaps not surprisingly. maternal consumption of a high saturated fat diet during pregnancy compounds the problem. The primary aims of the studies reported in this thesis were to investigate the effect of: (a) matemal diabetes on placental fatty acid composition in human subjects, and (b) matemal diabetes and a high saturated fat intake on tissue composition of the offspring in laboratory animal model. Therefore. the key objectives of this thesis were to: (1) . analyse human placental fatty acids from healthy pregnancies at two times in gestation. early (8-14 wk) and term (38- 41wk). (2) compare placental fatty acids from pregnant women with gestational diabetes mellitus (GDM) and women who delivered preterm with the healthy term placenta, and (3) investigate the effects of maternal diabetes and/or a high fat diet during pregnancy on the fatty acid composition of the vascular tissues, particularly arachidonic (AA) and docosahexaenoic (DHA) acids of the offspring. The main outcomes of these investigations were that: (1) AA was incorporated in high proportions (17.2-35.9%) in most phospholipids. At term. AA was reduced in choline (CPG). ethanolamine (EPG) and inositol (IPG) phosphoglycerides while di-hommo-ylinolenic acid (DGLA) was markedly increased in CPG, EPG, IPG and serine (SPG) phosphoglycerides compared with early in gestation (8-14wk) placental membranes, (2) the GDM placenta had elevated AA and DHA in CPG and EPG while the preterm placenta had reduced DHA in CPG and SPG and AA in SPG, and (3) maternal diabetes reduced AA and arachidonic-to linoleic acid ratio (AAlLA) in the offspring. Similarly, feeding dams to a 32.9%-fat or 20%-fat (mainly lard) diet reduced DHA in liver and heart CPG and EPG or AA and DHA in aorta CPG and EPG of the offspring. The high dominance of AA, particularly in the membranes of the early placenta, may suggest that AA has an important role for placental development - organogenesis and vascularisation. Conversely. the enrichment of placental membranes with DGLA at term is more consistent with a profile favouring optimal blood flow to nourish the fetal growth spurt. On the other hand, maternal diabetes and preterm delivery led to a compromised M and DHA placental content. The experimental data strongly support the hypotheSiS that disturbance in utero environment through inadequate maternal essential fatty acid lipid nutrition impaired tissue synthesis DHA and/or AA in the offspring and. hence. may set the offspring at high risk for the development of cardiovascular disorders later in life.
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