Oviductal extracellular vesicles from women with endometriosis impair embryo development
Objective To investigate the influence that oviductal extracellular vesicles from patients with endometriosis exert on early embryo development. Design In vitro experimental study Setting University-affiliated hospital. Patient(s) Women with and without endometriosis who underwent hysterectomy (n = 15 in total). Intervention(s) None. Main Outcome Measure(s) Oviductal extracellular vesicles from patients with endometriosis (oEV-EMT) or without endometriosis (oEV-ctrl) were isolated and co-cultured with two-cell murine embryos for 75 hours. Blastocyst rates were recorded. RNA sequencing was used to identified the differentially expressed genes in blastocysts cultured either with oEV-EMT or with oEV-ctrl. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to identify potential biological processes in embryos that oEV-EMT affect. The functions of oEV on early embryo development were determined by reactive oxygen species (ROS) levels, mitochondrial membrane potentials, total cell numbers and apoptotic cell proportions. Result(s) Extracellular vesicles were successfully isolated from human Fallopian tubal fluid and their characterizations were described. The blastocyst rates were significantly decreased in the oEV-EMT group. RNA sequencing revealed that oxidative phosphorylation was down-regulated in blastocysts cultured with oEV-EMT. Analysis of oxidative stress and apoptosis at the blastocysts stage showed that embryos cultured with oEV-EMT had increased ROS level, decreased mitochondrial membrane potentials, and increased apoptotic index. Total cell numbers were not influenced. Conclusion(s) Oviductal extracellular vesicles from patients with endometriosis exert a negative influence on early embryo development. Overall design: Extracellular vesicles were isolated from human Fallopian tubal fluid. Murine embryos were co-cultured with these extracellular vesicles. Blastocysts were sequenced.