摘要Background Oxidative stress(OS)is involved in low female fertility by altering multi-omics such as the transcriptome,miRome,and lncRNome in follicular cells and follicular fluid.However,the mechanism by which OS affects multi-omics dynamics remains largely unknown.Here,we report that OS induces lncRNome dynamics in sow granulosa cells(sGCs),which is partially dependent on the transcription factor activity of its effector,FoxO1.Results A total of 2,283 putative FoxO recognition elements(FREs)were identified in the promoters of 394 lncRNAs,accounting for 91.20％(394/432)of the lncRNAs regulated by OS.ChIP and reporter assays showed that the effec-tor FoxO1 mediated OS regulation of lncRNA transcription in a transcription factor activity-dependent manner.In sGCs,OS induces the transcription and function(e.g.,apoptosis)of NORSF(non-coding RNA involved in sow fertility),a nuclear lncRNA involved in sGC function via FoxO1.Furthermore,FoxO1 has been identified as a transcriptional acti-vator of NORSF in sGCs that interacts with the FRE motif of its promoter.Meanwhile,OS downregulates the transcrip-tion of CYP19A1,which encodes an essential enzyme for estrogen synthesis and 17β-estradiol(E2)release by sGCs via the FoxO1 and NORSFaxis.Phenotypically,dysregulation of NORSF transcription caused by 2 novel adjacent transi-tions in the promoter leads to decreased sow fertility.Conclusion These results suggest a model of OS-stimulated lncRNome dynamics in sGCs and a new signaling path-way of OS that influences sGC function and sow fertility.