〔Abstract〕 Objective To explore the mechanism of chronic prenatal stress inducing depression in offspring male rats.Methods Thirty pregnant rats were randomly divided into the control group and the chronic unpredictable mild stress group(CUMS). After the rats were born, male offspring rats were randomly divided into the control + Solvent group(CON group), the control + CRHR1 antagonist group(CON+ANT group), the CUMS + CRHR1 antagonist group(CUMS+ANT group) and the CUMS+Solvent group(CUMS group). Solvent or CRHR1 antagonist were administered by lateral ventricle injection to 10～30-day-old rats. Then we observed depressive-like behaviors, number and morphology of hippocampal CA3 neurons, the level of corticotrophin-releasing hormone(CRH) in the hippocampus, mammalian target of rapamycin(mTOR) and p-mTOR(Ser2448) protein expression. Hippocampal slices of 10-day-old rats were cultured in vitro, and slices were divided into the control group(Control group),1.0 μmol/L CRH+different dose of CRHR1 antagonist group and 1.0 μmol/L CRH+solvent control group(CRH group).Western blot was used to observe the expression of mTOR protein.Results Compared with the CON group,the offspring rats in CUMS group had more motion time in forced swimming test( P<0. 05) and less sugar preference rate in the sugar preference test( P<0. 05). The hippocampus CRH concentration increased( P<0. 05) and the neuropathological changes were characterized by decreased neuron number,loosed neurons and the soma condensation in CA3 field of hippocampus. Moreover,the expression of m TOR and p-m TOR both decreased in hippocampus( P<0. 05). Compared with the CUMS group,the offspring rats in CUMS + CRHR1 antagonist group had less motion time in forced swimming test( P<0. 05) and more sugar preference rate in the sugar preference test( P<0. 05). The level of CRH in hippocampus was down-regulated,the neuropathological damage in hippocampus CA3 region was improved and the expression of m TOR and p-m TOR both increased( P<0. 05). The results of hippocampal slicesculture showed that the expression of m TOR decreased more in CRH group than that in Control group( P<0. 05). Low,middle and high concentration of CRHR1 antagonist could upregulate the decreased level of m TOR induced by CRH( P<0. 05). Conclusion Depression of male offspring caused by chronic prenatal stress may be associated with the increased level of CRH in the hippocampus which inhibit the expression of m TOR protein and cause the neuropathological damage in the CA3 field of hippocampus.