〔Abstract〕 Objective To investigate the sex difference of the effects of chronic pregnancy stress on depression-like behavior in offspring adolescent mice and whether the amygdala is involved in mediating depression-like behavior and its possible mechanism. Methods Male and female of C57 BL/6 J mice were put in cage together. Pregnant mice were randomly divided into normal control group(CON group) and chronic pregnancy stress group(CPS group). The day of delivery was recorded as post-natal day(PND0). The offspring of different groups were divided into Female group and Male groupaccording to sex, respectively. From PND35, the depressive-like behavior of offspring was monitored in different groups. Morphological structure of basolateral amygdala(BLA)cone neurone was observed by Golgi-Cox staining, and apoptosis of BLA neurone was detected by TUNEL.Serum corticotrophin-releasing hormone(CRH)was detected by ELISA. The level of protein associated with amygdala mammalian target of rapamycin(mTOR) and phosphorylated mammalian target of rapamycin [p-mTOR(Ser2448)] was detected by Western blot. Results Depression-like behavior was appeared in different sexual offspring by chronic pregnancy stress, and there was an interaction between chronic pregnancy stress and gender. In the forced swimming test, the immobility time of offspring in the CPS group prominently increased(Female:P<0.05,Male:P<0.001). Interestingly, compared with female offspring, despairing behavior of male offspring was much more clearly observed in CPS group(P<0.05). Compared with offspring of CON group, the rate of sucrose preference was significantly reduced in the female offspring of CPS group(P<0.05), while no obvious difference was observed in the male offspring. Compared with the CON group, the density of neuronal dendrite branches in the BLA of offspring mice in the CPS group decreased(Female:P<0.01,Male:P<0.01) and the degree of neuronal apoptosis increased(Female:P<0.001,Male:P<0.001), the expression level of p-mTOR in amygdala of offspring mice in CPS group significantly decreased(Female:P<0.001,Male:P<0.001). Chronic pregnancy stress increased the serum CRH level of offspring mice(P<0.001), and the gender had significant influence on serum CRH level, the serum CRH level of female in CPS group was higher than that of male(P<0.05). Conclusion Chronic pregnancy stress leads to depression-like behavior in offspring adolescent mice, and the depression-like behavior has gender differences. In addition, chronic pregnancy stress leads to dendrite atrophy and apoptosis of BLA neurons in offspring mice, and the mechanism may be that the activation of mTOR in the amygdala of offspring mice is inhibited. CRH may be involved in mediating sex differences in depression-like behavior and BLA neuron damage in offspring induced by chronic pregnancy stress.