Increasing　evidence　has　shown　that　prenatal　stress　(PS)　could　cause　depression-like　behavior　in　the　offspring,　which　is　sex-specific.　However,　the　underlying　mechanisms　remain　to　be　elucidated.　This　study　is　to　investigate　the　involvement　of　tryptophan　hydroxylase　2　(Tph2)　H3K9　acetylation　(H3K9ac)　modification　on　PS-induced　depression-like　behavior　in　juvenile　offspring　rats　(JOR).　PS　models　were　established,　with　or　without　trichostatin　A　(TSA)　treatment.　Animal　behavior　was　assessed　by　the　sucrose　preference　test　(SPT)　and　forced　swimming　test　(FST).　The　mRNA　and　protein　expression　levels　of　TPH2　in　the　dorsal　raphenucleus　(DRN),　hippocampus,　and　prefrontal　cortex　were　detected　with　quantitative　real-time　PCR　and　Western　blot　analysis,　respectively.　The　Tph2　H3K9ac　levels　in　the　hippocampus　were　also　analyzed.　SPT　and　FST　showed　significantly　reduced　sucrose　preference　and　significantly　prolonged　immobility　in　PS-induced　male　juvenile　offspring　rats　(MJOR).　Moreover,　the　mRNA　and　protein　expression　levels　of　TPH2　in　the　DRN　and　hippocampus　were　significantly　declined,　while　the　hippocampal　Tph2　H3K9ac　levels　were　significantly　declined　in　the　PS-induced　MJOR.　Furthermore,　the　PS-induced　effects　in　MJOR　could　be　reversed　by　the　microinjection　of　TSA.　However,　no　significant　effects　were　observed　for　the　female　juvenile　offspring　rats　(FJORs).　In　conclusion,　our　results　showed　that　the　Tph2　H3K9ac　modification　is　only　involved　in　PS-induced　depression-like　behavior　in　MJOR,　in　a　sex-specific　manner.　These　findings　might　contribute　to　the　understanding　of　the　disease　pathogenesis　and　clinical　treatment　in　future.　(C)　2018　IBRO.　Published　by　Elsevier　Ltd.　All　rights　reserved.