Single-Cell Analysis of Ovarian Endometriosis-Associated Infertility

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Abstract

Endometriosis, particularly ovarian endometriosis (OE), significantly impairs fertility, often leading to reduced oocyte quality and compromised ovarian function. Iron overload has been identified as a key factor driving the progression of endometriosis. This study aims to investigate the impact of iron overload on follicular function in OE-associated infertility (OEI). Using single-cell RNA sequencing, we first confirmed the impaired oocyte function in OEI patients and established a single-cell atlas of iron overload in pre-ovulatory follicular fluid from these patients, revealing dynamic changes in iron metabolism and identifying iron accumulation-induced senescence phenotypes. We also explored the differentiation trajectories of cumulus cells and the relationship between macrophage M1/M2 phenotypes and iron metabolism. Furthermore, we employed Stereo-seq to construct a spatial transcriptomic map of iron-overloaded mouse ovaries, uncovering various enriched senescence phenotypes. Finally, we extended our findings by investigating the dynamics of iron metabolism imbalance in aging human ovaries. Collectively, these findings deepen our understanding of iron overload-related cellular interactions and molecular features in ovarian pathology, offering new therapeutic targets for improving oocyte quality in OEI patients.
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Single-Cell Analysis of Ovarian Endometriosis-Associated Infertility Source: CNGBdb Project (ID CNP0006183) Source: CNGBdb Project (ID CNP0006183) 0 0 Description: Endometriosis, particularly ovarian endometriosis (OE), significantly impairs fertility, often leading to reduced oocyte quality and compromised ovarian function. Iron overload has been identified as a key factor driving the progression of endometriosis. This study aims to investigate the impact of iron overload on follicular function in OE-associated infertility (OEI). Using single-cell RNA sequencing, we first confirmed the impaired oocyte function in OEI patients and established a single-cell atlas of iron overload in pre-ovulatory follicular fluid from these patients, revealing dynamic changes in iron metabolism and identifying iron accumulation-induced senescence phenotypes. We also explored the differentiation trajectories of cumulus cells and the relationship between macrophage M1/M2 phenotypes and iron metabolism. Furthermore, we employed Stereo-seq to construct a spatial transcriptomic map of iron-overloaded mouse ovaries, uncovering various enriched senescence phenotypes. Finally, we extended our findings by investigating the dynamics of iron metabolism imbalance in aging human ovaries. Collectively, these findings deepen our understanding of iron overload-related cellular interactions and molecular features in ovarian pathology, offering new therapeutic targets for improving oocyte quality in OEI patients. Data type: Raw sequence reads Sample scope: Multispecies Relevance: Medical Submitter: 李杨硕(Yangshuo Li); 海军军医大学附属长海医院 Literatures - PMID: 40693455 Release date: 2025-06-30 Last updated: 2025-06-30 DOI: 10.26036/CNP0006183 Data size: 471.01GB

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