Integrative Single-Cell Analysis Reveals Iron Overload-Induced Senescence and Metabolic Reprogramming in Ovarian Endometriosis-Associated Infertility.

Adv Sci (Weinh), 2025/8;12(29):e17528.

Li Y[1], Zhou W[2], Ding J[1], Song D[3], Cheng W[1], Yu J[1], Sun S[1], Mei S[4], Liang X[1], Zhao Q[1], Kuang Y[5], Li M[6], Ni Z[2], Yu C[1], Gao Y[2]

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PMID: 40693455DOI: 10.1002/advs.202417528

Impact factor: 17.521

Abstract
Endometriosis, particularly ovarian endometriosis (OE), is a major cause of infertility, often associated with reduced oocyte quality and impaired ovarian function. Iron overload plays a key role in OE progression. This study investigates the effects of iron overload on follicular function in OE-associated infertility (OEI). A single-cell atlas of pre-ovulatory follicular fluid from OEI patients reveals dynamic changes in iron metabolism and iron-induced senescence phenotypes. Spatial transcriptomics using Stereo-seq in iron-overloaded mouse ovaries further identifies localized senescence features. Additional analysis of aging human ovaries highlights conserved patterns of iron dysregulation. These findings provide mechanistic insight into iron overload-related ovarian pathology and suggest potential therapeutic targets for improving oocyte quality in OEI.

Keywords: endometriosis; infertility; iron; multi‐omics; senescence

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