〔Abstract〕 Objective To investigate the mechanism of chronic stress during pregnancy inducing depression in male offspring mice. Methods 8-week-old female C57 mice containing pure flox gene [flox/flox, corticotropin-releasing hormone receptor1(CRHR1) gene normal expression] and male C57 mice containing heterozygous flox gene and containing cre gene(flox/+, with cre; CRHR1 gene conditions Sex knockout) were put in cage together.The pregnant mice were randomly divided into the control group and the chronic stress group. After the mice were born,the male offspring mice were randomly divided into the control group( CON group),the control + CRHR1 gene knockout heterozygous mice group( CON + CKOH group),the control + CRHR1 gene knockout homozygous mice group( CON + CKOA group),the chronic unpredictable mild stress group( CUMS group),the chronic unpredictable mild stress + CRHR1 gene knockout heterozygous mice group( CUMS + CKOH group),the chronic unpredictable mild stress + CRHR1 gene knockout homozygous mice group( CUMS + CKOA group). The degree of depression in male offspring mice was observed by sucrose preference experiment,tail suspension experiment and forced swimming experiment. TUNEL staining was used to observe apoptosis in hippocampal CA3 area. Western blot was used to quantitatively detect the expression of m TOR and p-mTOR( Ser2448) in hippocampus. Results Chronic stress during pregnancy induced depression-like behavior,increased neuronal apoptosis index in hippocampal CA3 area,and attenuated the level of hippocampal m TOR and p-mTOR protein significantly in male offspring mice. Hippocampal CRHR1 gene conditional knockout could significantly improve depressive-like behavior,neuronal apoptosis in the hippocampus CA3 region and the levels of m TOR and p-mTOR proteins in the male offspring mice whose mother suffered from chronic stress during pregnancy. Conclusion Chronic stress during pregnancy can lead to depression-like behavior in male offspring mice through activating CRHR1 of hippocampus and attenuating m TOR protein expression in the hippocampus,which results in neuronal injury in the CA3 region of offspring hippocampus.