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

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.