Effects of docosahexaenoic acid supplementation on global gene expression in fetal brain in rats exposed to ethanol prenatally
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Prenatal alcohol exposure is known to change genes involved in signal transduction and neurological system processes, thus affecting normal fetal brain development. Omega-3 docosahexaenoic acid (DHA), a major component of brain, is known to be decreased in brain with alcohol consumption justifying its provision is necessary with alcohol exposure during pregnancy. This study was planned to examine if DHA supplementation impacts on global gene expressions in fetal brain exposed to ethanol during entire gestation period. Upon pregnancy, Sprague Dawley rats were raised on a control diet (Cont), Cont+Ethanol (EtOH, 6g/kg body weight, via gavage), or EtOH+DHA supplementation (1.4%, w/w, total fat) during gestational period. The diet was semi-purified nutritionally complete-energy dense (4.3 Kcal/g diet), reflecting typical intake of Canadians pregnant women. The global gene expression in the fetal brain (n=5 each group, 1-2 from each dam) in gestational day 20 was analysed by microarray and real-time polymerase chain reaction (qRT-PCR) for validation. The protein expression was analysed by Western blot. No significant differences were identified in the fetal brain and body weights among the groups. Microarray analysis revealed that none of the transcripts were significantly altered in fetus brain (Log2(fold change) ≤ ± 2, and P > 0.05). qRT-PCR, agreed with microarray data in fold changes (FC<2 or FC>0.5). DHA supplementation significantly (p<0.05) decreased the increased expression of PCDHB6 with EtOH, to the levels in the Cont group. EtOH also decreased WDR92 expression regardless of a DHA provision in comparison to the Cont. EtOH+DHA significantly decreased the expression of NFIA, NEUROD1, GRIN1 and WDR92 in comparison to the Cont. Western blot revealed that none of the proteins expressed significantly different among the groups. These findings indicate that the DHA supplementation have minor impacts on global gene expressions in the fetal brain exposed to ethanol during entire gestation period. It is speculated that the nutrient dense diet provided in this study may have mitigated the effects of ethanol. Future studies can be aimed at studying global gene expression with low vs high energy dense diet.