Ovarian Endometrioma Disrupts Oocyte‐Cumulus Communication and Mitochondrial Function, With Melatonin Mitigating the Effects

Abstract

ABSTRACTOvarian endometrioma (OEM), a particularly severe form of endometriosis, is an oestrogen‐dependent condition often associated with pain and infertility. The mechanisms by which OEM impairs fertility, particularly through its direct impact on oocyte‐cumulus cell (CC) communication and related pathways, remain poorly understood. This study investigates the impact of OEM on oocyte‐CC communication and explores melatonin's therapeutic potential. We used a mouse model of OEM and employed ovarian transcriptome and gene set enrichment analyses to identify disrupted gene pathways, alongside phalloidin staining for cytoskeletal analysis, gap junction coupling analysis for intercellular communication, and mitochondrial function assessments for cellular metabolism. Our results showed that OEM significantly impairs steroidogenesis and cumulus cell function, leading to increased apoptosis, disrupted transzonal projections (TZPs), and impaired antioxidant transfer to oocytes. This culminates in oxidative stress, mitochondrial dysfunction, and compromised ATP production. OEM oocytes also exhibited severe abnormalities, including DNA damage, maturation defects, spindle assembly disruptions, and increased aneuploidy. This study identifies disrupted TZPs as a key pathological feature in OEM and highlights melatonin's potential to restore intercellular communication, mitigate oxidative damage, and improve reproductive outcomes.