Single-cell transcriptomic profiling unveils insights into ovarian fibrosis in obese mice.

Autor: Xiao B; Department of Medical Genetics, Naval Medical University, 800 Xiang yin Road, Shanghai, 200433, China., Dai Z; Department of Medical Genetics, Naval Medical University, 800 Xiang yin Road, Shanghai, 200433, China., Li Z; Translational Medicine Research Center, Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital, 51 Fu cheng Road, Beijing, 100853, China., Xu D; Department of Reproductive Medicine, Second Affiliated Hospital of Naval Medical University, 415 Feng yang Road, Shanghai, 200003, China., Yin H; Department of Medical Genetics, Naval Medical University, 800 Xiang yin Road, Shanghai, 200433, China., Yang F; Department of Medical Genetics, Naval Medical University, 800 Xiang yin Road, Shanghai, 200433, China. yangfusq1997@smmu.edu.cn.; Department of Reproductive Medicine, Second Affiliated Hospital of Naval Medical University, 415 Feng yang Road, Shanghai, 200003, China. yangfusq1997@smmu.edu.cn., Sun N; Department of Reproductive Medicine, Second Affiliated Hospital of Naval Medical University, 415 Feng yang Road, Shanghai, 200003, China. suesunchzh@126.com.
Jazyk: angličtina
Zdroj: Biology direct [Biol Direct] 2024 Jul 02; Vol. 19 (1), pp. 52. Date of Electronic Publication: 2024 Jul 02.
DOI: 10.1186/s13062-024-00496-9
Abstrakt: Background: Adiposity profoundly impacts reproductive health in both humans and animals. However, the precise subpopulations contributing to infertility under obese conditions remain elusive.
Results: In this study, we established an obese mouse model through an eighteen-week high-fat diet regimen in adult female mice. Employing single-cell RNA sequencing (scRNA-seq), we constructed a comprehensive single-cell atlas of ovarian tissues from these mice to scrutinize the impact of obesity on the ovarian microenvironment. ScRNA-seq revealed notable alterations in the microenvironment of ovarian tissues in obese mice. Granulosa cells, stromal cells, T cells, and macrophages exhibited functional imbalances compared to the control group. We observed heightened interaction strength in the SPP1-CD44 pairing within lgfbp7 + granulosa cell subtypes and Il1b high monocyte subtypes in the ovarian tissues of obese mice. Moreover, the interaction strength between Il1b high monocyte subtypes and Pdgfrb + stromal cell subtypes in the form of TNF - TNFrsf1α interaction was also enhanced subsequently to obesity, potentially contributing to ovarian fibrosis pathogenesis.
Conclusions: We propose a model wherein granulosa cells secrete SPP1 to activate monocytes, subsequently triggering TNF-α secretion by monocytes, thereby activating stromal cells and ultimately leading to the development of ovarian fibrosis. Intervening in this process may represent a promising avenue for improving clinical outcomes in fertility treatments for obese women.
(© 2024. The Author(s).)
Databáze: MEDLINE
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