The inconsistent pathogenesis of endometriosis and adenomyosis: insights from endometrial metabolome and microbiome

mSystems, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

ABSTRACT Endometriosis (EM) and adenomyosis (AM) are interrelated gynecological disorders characterized by the aberrant presence of endometrial tissue frequently linked with chronic pelvic pain infertility, yet their pathogenetic mechanisms remain largely unclear. In this cross-sectional study, we analyzed samples from 244 participants, split into 91 EM patients, 56 AM 97 healthy controls (HC). We conducted untargeted liquid chromatography-mass spectrometry (LC-MS) 5R 16S rRNA sequencing to examine metabolome microbiome profiles. Additionally, integrated transcriptomic analysis using nine data sets investigate biological basis these conditions. Metabolomic profiling revealed distinct metabolic microbial signatures. Specific pathways, including linoleic acid glycerophospholipid metabolism, show significant alterations in both Notably, four metabolites, phosphatidylcholine 40:8 [PC(40:8)], exhibited marked changes AM, suggesting shared pathological features. Furthermore, taxonomic identified unique bacterial species associated each condition, particularly those belonging phylum Proteobacteria, which correlated altered Machine learning models demonstrated high predictive accuracy for differentiating between EM, HC based on Integrative highlighted pathways related immune response signaling transduction condition. Our study provides fresh insights pathogenesis through a multi-omic approach, potential inconsistencies underlying mechanisms. IMPORTANCE Existing research connection endometriosis (AM), underscoring overlapping symptoms pathophysiological Although role microbiota inflammatory conditions has been acknowledged, comprehensive investigations cases have limited. Previous studies communities conditions; however, they were constrained small sample sizes lack analyses metabolomics. ongoing debate over whether should be classified as separate diseases or phenotypes emphasizes necessity further exploration molecular interactions. uncovers signatures revealing that may contribute pathogenesis. integration offers valuable complex interactions disorders.

Language: Английский

The antioxidant property of CAPE depends on TRPV1 channel activation in microvascular endothelial cells.

Redox Biology, Journal Year: 2025, Volume and Issue: 80, P. 103507 - 103507

Published: Jan. 20, 2025

Caffeic acid phenethyl ester (CAPE) is a hydrophobic phytochemical typically found in propolis that acts as an antioxidant, anti-inflammatory and cardiovascular protector, among several other properties. However, the molecular entity responsible for recognising CAPE unknown, whether interaction involved developing antioxidant response target cells remains unanswered question. Herein, we hypothesized subfamily of TRP ion channels works recognizes at plasma membrane allows fast shift capacity intact endothelial (EC). By monitoring cytoplasmic Ca2+ microvascular EC model, compared calcium responses evoked by three structurally related compounds: caffeic ester, neochlorogenic acid. Only induced rapid transient nanomolar concentrations together with gradual increase sodium levels, suggesting activation non-selective cationic permeation membrane. Electrophysiological well pharmacological, RNA silencing assays confirmed involvement TRPV1 recognition ECs. Finally, demonstrated influx was necessary recording CAPE-induced redox changes, phenomenon captured real-time ECs expressing HyPer biosensor. Our data depict mechanism behind effect cells, connecting channels, increase, reduction disulfide bonds on This occurs within seconds to minutes contributes better understanding mechanisms underlying vasodilatory compounds interact vascular bed.

Language: Английский