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

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

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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 tran-scription 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.

obesityovarian microenvironmentsnRNA-seqStereo-seqFoxo1

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

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Center for Reproductive Medicine,Shandong University,Jinan 250012,China

Key Laboratory of Reproductive Endocrinology of Ministry of Education,Shandong University,Jinan 250012,China

Shandong Key Laboratory of Reproductive Medicine,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250012,China

Shandong Provincial Clinical Research Center for Reproductive Health,Jinan 250012,China

National Research Center of Assisted Reproductive Technology and Reproductive Genetics,Shandong Un

Research Unit of Gametogenesis and Health of ART-Offspring,Chinese Academy of Medical Sciences(No.2021RU001),Jinan 250012,China

Shandong Provincial Clinical Research Center for Reproduct

State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Science,Beijing 100101,China

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National Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaCAMS Innovation Fund for Medical SciencesShandong Provincial Key Research and Development ProgramTaishan Scholars Program of Shandong ProvinceFundamental Research Funds of Shandong University

2021YFC27004002018YFC100430331988101822017988219287482071606821017072021-12M-5-0012020ZLYS02ts20190988

2024

10.1007/s11427-023-2360-3

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子：0.806
ISSN：1674-7305
年,卷(期)：2024.67(1)
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