Ntf3 hypermethylation in antenatal PTSD and preventive effect of the Chinese herbal medicine Jin Kui Shen Qi Wan

Antenatal post-traumatic stress disorder (PTSD can leave offspring with life-long mental and behavioural disorders. This study investigated the epigenetic mechanism of the effects of Jin Kui Shen Qi Wan (JKSQW) in preventing antenatal PTSD. Thirty-six pregnant rats were randomized into Control, PTSD and JKSQW. Offspring characteristics were investigated with open-field test (OFT), elevated pull maze (EPM), gene expression profile chip test and methylated DNA immunoprecipitation sequencing. In the OFT test, the PTSD offspring showed lower OFT scores than the Control and JKSQW groups (p < 0.05). The PTSD group's EPM performance, OE (open arm entry) + CE (closed arm entry), OE% and OT% (open arm time) were also lower than those of either the Control or the JKSQW group (p < 0.05). In the gene expression profile chip test, 54 genes showed dysregulation through PTSD intervention and were normalized by JKSQW. Endocytosis (Epn3, Folr1 and Hspall) and MAPK signaling (Fgf17, Hspall, Ntf3 and Pla2g5) pathways were annotated. Combining those genes and methylation sequencing, Ntf3 was identified in both tests. Compared with the Control, the PTSD offspring showed Ntf3 hypermethylation (Log(2)FC = 1.022) at 225679501 similar to 225680000 on Chromosome 4 and downregulation in the gene expression profile. The Ntf3 methylation level in JKSQW was restored nearly to the Control level (Log(2)FC = -1.082 in JKSQW vs. PTSD). In conclusion, the reduction in the offspring's behavioural performance might constitute experimental evidence of kidney deficiency due to Ntf3 hypermethylation, which could be prevented by JKSQW.