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作者

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

作者单位

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

刊名

Science China(Life Sciences)

年份

2024

卷号

第67卷

期号

第1期

页码

51-66

ISSN

1674-7305

分类号

R589.2

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. 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 i...更多

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. 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 induced obesity and Leptin ablation induced obesity. 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 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.收起

基金

国家自然科学基金

文献类型

期刊