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Updated: Jan 11, 2026
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Cell-Specific Paired Interrogation of the Mouse Ovarian Epigenome and Transcriptome
Published on: February 24, 2023
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Spatial Transcriptomic Characteristics of the Aging Human Ovary.
Meiling Zhang1,2, Fanghao Guo1,2, Qing Zhang1,2,3
1Center for Reproductive Medicine & Fertility Preservation Program, International Peace Maternity and Child Health Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai, China.
Aging Cell
|November 17, 2025
Summary
Human ovarian aging impairs fertility by altering cell function and connectivity. A novel endothelial cell subtype shows increased inflammatory activity with age, highlighting potential therapeutic targets for reproductive disorders.
Area of Science:
- Reproductive biology and aging research.
- Genomics and transcriptomics.
- Cellular and molecular mechanisms of aging.
Background:
- Ovarian aging is a complex biological process impacting female fertility and increasing risks for reproductive health issues.
- Understanding the spatiotemporal dynamics of ovarian aging is crucial for addressing age-related fertility decline and disorders.
- Existing research lacks a comprehensive atlas detailing cellular and molecular changes throughout human ovarian aging.
Purpose of the Study:
- To construct a comprehensive aging atlas of human ovarian tissues across a wide age range.
- To elucidate the spatiotemporal dynamics and molecular mechanisms underlying human ovarian aging.
- To identify novel cell types and molecular pathways involved in ovarian aging and associated disorders.
Main Methods:
- Integrated single-nucleus RNA sequencing and spatial transcriptomics.
- Analyzed 12 human ovarian tissues from individuals aged 12 to 54 years.
- Utilized transcriptomic and spatial mapping to identify cellular and molecular changes.
Main Results:
- Identified aging-related transcriptomic shifts, including impaired mitochondrial function and reproductive structure development.
- Discovered a novel endothelial cell (EDC) subtype, CLDN5+ blood EDCs, with enhanced antigen-presenting and inflammatory functions in aged ovaries.
- Revealed disrupted cellular connectivity and amplified DLK1:NOTCH3 axis, with DLK1 upregulation in granulosa cells of patients with primary ovarian insufficiency.
Conclusions:
- Human ovarian aging involves significant transcriptomic alterations and disrupted cellular interactions.
- CLDN5+ blood EDCs exhibit age-sensitive inflammatory and antigen-presenting roles, suggesting their involvement in ovarian aging.
- The study provides insights into ovarian aging mechanisms and identifies potential therapeutic targets for reproductive disorders.
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