Transcriptional and epigenetic changes of brain derived neurotrophic factor following prenatal stress: A systematic review of animal studies

•PNS causes decreased or unchanged BDNF mRNA and BDNF mature protein in fetal brain.•PNS causes hyper methylation of the coding exons of BDNF in the fetal brain.•Stress paradigm, gender of the fetus and day of the sacrifice affect outcomes.•Hippocampus and PFC are the most vulnerable regions to PNS. Gestational period plays critical role in neuropsychological development. One of the genes that undergoes changes by prenatal stress (PNS) exposure, is the gene coding brain derived neurotrophic factor (BDNF). Studies have reported different patterns of change following PNS in BDNF, which emphasizes the complexity of the issue. In this review, systematic search of PubMed, Scopus, Web of Science and Cochrane CENTRAL databases was performed. Primary searches resulted in 2132 studies and finally 43 studies were found to meet the inclusion criteria. Transcriptional and epigenetic changes of BDNF gene in the brain were recorded. Decreased or unchanged BDNF total mRNA and BDNF mature protein, with hypermethylation of the coding exons were the most reported changes. However, stress paradigm, gender of the fetus and the day of sacrifice were found to significantly affect the results. Hippocampus and prefrontal cortex are the most vulnerable regions. They can show long lasting and persistent transcriptional and epigenetics changes of BDNF gene following PNS. Further studies evaluating the importance of these findings in humans are essential.