Effects of Oestradiol on Brain Lipid Class and Fatty Acid Composition: Comparison Between Pregnant and Ovariectomised Oestradiol-Treated Rats

To determine the involvement of physiological doses of oestradiol on brain lipid composition, we have analysed the lipid class and fatty acid composition of phospholipids in the brain from pregnant and 17 beta-oestradiol-treated rats. Rats were randomly divided into three groups: ovariectomised control (OVX + VEH), ovariectomised oestradiol-treated (OVX + E-2) and pregnant (PREG) rats. Rats from the OVX + E-2 group were injected daily with different doses of 17 beta-oestradiol mimicking the plasma levels observed during pregnancy. Analyses of brain lipid class composition showed that physiological doses of oestradiol increased cholesterol levels of the OVX + E-2 group compared to the OVX + VEH group. It was also found that cholesterol levels in the PREG group were significantly lower than in the OVX + VEH and OVX + E-2 groups, indicating the involvement of gestational hormones other than oestradiol in the regulation of brain cholesterol during pregnancy. Brains from pregnant rats also exhibited reduced levels of plasmalogens and saturated fatty acids compared to the ovariectomised groups, especially in the second half of pregnancy. Interestingly, analyses of fatty acid composition of phospholipids revealed that physiological doses of oestradiol increased brain docosahexaenoic acid (DHA; 22:6 n-3) levels. Moreover, DHA levels in pregnant rats were similar to those observed in the OVX + E-2 group at all stages, suggesting that oestradiol is the main hormone in the regulation of brain DHA levels during pregnancy. Liver appears to be the major source for n-3 and n-6 long chain polyunsaturated fatty acids (LCPUFAs) DHA and arachidonic acid, which are released and transported to the maternal brain and the developing foetus under the influence of oestrogens. We also observed that the largest depots of n-3 and n-6 LCPUFA precursors (linolenic acid and linoleic acid, respectively) occur in adipose tissue triglycerides, which, in turn are significantly increased during pregnancy. Our observations are in accordance with an oestradiol-induced increased bioavailability of brain DHA in pregnant rats. We hypothesise that the reduction of maternal brain DHA observed at the end of pregnancy is a result of the very high demand DHA of foetal brain, which overcomes the maximal maternal (and likely foetal) capacity for de novo DHA synthesis in the liver and brain.