Cellular atlases of ovarian microenvironment alterations by diet and genetically-induced obesity  

作　　者：Yonghui Jiang Xueying Gao Yue Liu Xueqi Yan Huangcong Shi Rusong Zhao Zi-Jiang Chen Fei Gao Han Zhao Shigang Zhao 

机构地区：[1]Center for Reproductive Medicine,Shandong University,Jinan 250012,China [2]Research Unit of Gametogenesis and Health of ART-Offspring,Chinese Academy of Medical Sciences(No.2021RU001),Jinan 250012,China [3]Key Laboratory of Reproductive Endocrinology of Ministry of Education,Shandong University,Jinan 250012,China [4]Shandong Key Laboratory of Reproductive Medicine,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250012,China [5]Shandong Provincial Clinical Research Center for Reproductive Health,Jinan 250012,China [6]National Research Center of Assisted Reproductive Technology and Reproductive Genetics,Shandong University,Jinan 250012,China [7]The Affiliated Suzhou Hospital of Nanjing Medical University,Suzhou Municipal Hospital,Gusu School,Nanjing Medical University,Suzhou 215000,China [8]Center for reproductive medicine,Ren Ji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200127,China [9]Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics,Shanghai 200127,China [10]State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Science,Beijing 100101,China

出　　处：《Science China(Life Sciences)》2024年第1期51-66,共16页中国科学（生命科学英文版）

基　　金：This work was supported by the National Key Research and Development Program of China(2021YFC2700400,2018YFC1004303);the National Natural Science Foundation of China(31988101,82201798,82192874,82071606,82101707);CAMS Innovation Fund for Medical Sciences(2021-I2M-5-001);Shandong Provincial Key Research and Development Program(2020ZLYS02);the Taishan Scholars Program of Shandong Province(ts20190988);the Fundamental Research Funds of Shandong University.

摘　　要：Obesity,which can arise from genetic or environmental factors,has been shown to cause serious damages to the reproductive system.The ovary,as one of the primary regulators of female fertility,is a complex organ comprised of heterogeneous cell types that work together to maintain a normal ovarian microenvironment(OME).Despite its importance,the effect of obesity on the entire ovary remains poorly documented.In this study,we performed ovary single-cell and nanoscale spatial RNA sequencing to investigate how the OME changed under different kinds of obesity,including high-fat diet(HFD)induced obesity and Leptin ablation induced obesity(OB).Our results demonstrate that OB,but not HFD,dramatically altered the proportion of ovarian granulosa cells,theca-interstitial cells,luteal cells,and endothelial cells.Furthermore,based on the spatial dynamics of follicular development,we defined four subpopulations of granulosa cell and found that obesity drastically disrupted the differentiation of mural granulosa cells from small to large antral follicles.Functionally,HFD enhanced follicle-stimulating hormone(FSH)sensitivity and hormone conversion,while OB caused decreased sensitivity,inadequate steroid hormone conversion,and impaired follicular development.These differences can be explained by the differential expression pattern of the transcription factor Foxo1.Overall,our study provides a powerful and high-resolution resource for profiling obesity-induced OME and offers insights into the diverse effects of obesity on female reproductive disorders.

关 键 词：OBESITY ovarian microenvironment snRNA-seq Stereo-seq FOXO1 

分 类 号：R589.2[医药卫生—内分泌]