Oviductal extracellular vesicles from women with endometriosis impair embryo development

Abstract

Objective: To investigate the influence of oviductal extracellular vesicles from patients with endometriosis on early embryo development. Design: In vitro experimental study Setting: University-affiliated hospital. Patients: Women with and without endometriosis who underwent hysterectomy (n = 27 in total). Interventions: None. Main outcome measures: 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 identify 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 affects. The functions of oEV on early embryo development were determined by reactive oxygen species (ROS) levels, mitochondrial membrane potentials (MMP), total cell numbers, and apoptotic cell proportions. Results: 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 levels, decreased MMP, and increased apoptotic index. Total cell numbers were not influenced. Conclusion: Oviductal extracellular vesicles from patients with endometriosis negatively influence early embryo development by down-regulating oxidative phosphorylation.