Oxidative stress controls lncRNA-mediated sow granulosa cell functions in a FoxO1-dependent manner  

作　　者：Wenmin Sheng Miaomiao Wang Yuqi Li Zhenyu Sun Xing Du Qifa Li 

机构地区：[1]College of Animal Science and Technology,Nanjing Agricultural University,Nanjing 210095,China

出　　处：《Journal of Animal Science and Biotechnology》2025年第2期565-576,共12页畜牧与生物技术杂志(英文版)

基　　金：supported by the National Key R&D Program of China(2022YFD1600903);the National Natural Science Foundation of China(32272842)。

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 multiomics 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 effector FoxO1 mediated OS regulation of lncRNA transcription in a transcription factor activity-dependent manner.InsGCs,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 activator of NORSF in sGCs that interacts with the FRE motif of its promoter.Meanwhile,OS downregulates the transcription of CYP19A1,which encodes an essential enzyme for estrogen synthesis and 17β-estradiol(E2)release by sGCs via the FoxO1 and NORSF axis.Phenotypically,dysregulation of NORSF transcription caused by 2 novel adjacent transitions 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 pathway of OS that influences sGC function and sow fertility.

关 键 词：FOXO1 Granulosa cell apoptosis NORSF Oxidative stress Sow fertility 

分 类 号：S828[农业科学—畜牧学]