Objective To simulate modern social stress using pre pregnancy chronic mild stress mode (CMS) and explore the mechanism of emotional, behavioral, and neurodevelopmental changes in male offspring of pre pregnancy liver qi stagnation female mice through CORT-BDNF ERK1/2 signaling cascade mediated hippocampal injury. This study aims to elucidate the impact of negative life events on offspring and the intervention mechanism of Shuyu Capsule.Method CMS stress was used to induce pre pregnancy depression in female rats (liver qi stagnation state), and intervention was given with Shuyu capsules and fluoxetine capsules. After screening, male rats were mated, with 12 male offspring selected from each group for behavioral testing and ELISA detection of serum CORT levels in each group of male offspring rats; WB detection of BDNF, ERK1/2, p-ERK1/2, CREB, and p-CREB protein content in hippocampus; RT-PCR was used to detect the expression of BDNF mRNA, ERK1 mRNA, ERK2 mRNA, and CREB mRNA in the hippocampus; To verify the effect of pre pregnancy CMS on the BDNF ERK1/2-CREB signaling pathway in offspring, and to investigate the key micro mechanisms of Shuyu Capsule intervention on the emotional and learning memory related behaviors of male offspring with pre pregnancy liver qi stagnation syndrome.Results Experimental results on behavioral evaluation and mechanism exploration of male offspring rats with pre pregnancy liver qi stagnation syndrome in female mice. The results of behavioral testing showed that the distance, number of entries, and duration of stay in the central area of the open field experiment in the offspring of the model group were significantly reduced (p<0.05, p<0.05, p<0.05); During the exploration period of the water maze experiment, the escape latency was significantly prolonged (p<0.05), and the swimming distance, duration of the target quadrant, and number of platform crossings were reduced (p<0.05, p<0.05, p<0.01); The suspension time and frequency of the forced swimming experiment increased (p<0.05, p<0.01), and the incubation period shortened (p<0.05). After prophylactic treatment with Shuyu capsules and fluoxetine, the depression like behavior and cognitive impairment in the offspring of the model group were improved and corrected. The biochemical test results showed that the content of corticosterone in the offspring of the CMS model group increased (p<0.05); The protein content of BDNF, p-ERK1/2, and p-CREB in the offspring hippocampus decreased (p<0.05, p<0.05, p<0.05), and the expression of BDNF mRNA, ERK1 mRNA, ERK2 mRNA, and CREB mRNA was significantly reduced (p<0.01, p<0.05, p<0.01, p<0.05). After intervention treatment with Shuyu capsules and fluoxetine, the CORT content, BDNF, ERK1/2, CREB protein and mRNA expression in male offspring of female mice showed varying degrees of increase.Conclusion High levels of CORT in offspring selectively act on the hippocampus, exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF ERK1/2 signaling cascade. Chinese medicine Shuyu capsules can reduce the impact of adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.