Characteristics of Exosomes and Microbiota in the Decidua of Patients With Early Pregnancy Loss and Their Impact on Trophoblast Cells

Early pregnancy loss (EPL) is a common complication with incompletely understood pathogenesis. Recent studies highlight the roles of exosomes and their miRNAs in intercellular communication, and the influence of uterine decidual microbiota on pregnancy outcomes. This study aimed to characterize decidual exosomes and microbiota in EPL patients and explore their mechanistic roles in EPL development. Exosomes were extracted from decidual tissues of women undergoing normal pregnancy termination (NC group) and those with early pregnancy embryonic loss (EPL group). These exosomes were applied to treat trophoblast cells (HTR8/SVneo), and cell functions were examined using CCK-8, Transwell assays, and Annexin V-PI staining. Inflammation-related gene expression was quantified by qRT-PCR. Microarray analysis identified differentially expressed exosomal miRNAs, validated by qRT-PCR. 16S rRNA sequencing analyzed microbial community differences between groups, with key taxa identified using LEfSe. The roles of miR-483-5p mimics on Lactobacillales and trophoblast cells were also examined. Exosomes from both groups expressed CD63, HSP70, and Histone-H3, with typical membrane structures observed and particle sizes of 100-120 nm. Exosomes from the EPL group remarkably repressed trophoblast cell proliferation, migration, and invasion, promoted apoptosis, and upregulated TLR4, NF-κB, IL-6, TNF-α, and IL-8 mRNA levels. Microarray analysis revealed significant downregulation of miR-483-5p in exosomes from the EPL group. 16S rRNA sequencing showed distinct microbial communities in decidual tissues of the EPL group, particularly in Lactobacillales and Erysipelotrichaceae abundance. Hsa-miR-483-5p mimics enhanced Lactobacillales viability and colocalized with them. Combined treatment with miR-483-5p mimics and Lactobacillales reversed the inhibitory effects of exosomes from the EPL group on trophoblast cells and downregulated inflammatory factor expression. This study characterized exosomes in the decidual tissues of the EPL group and their inhibitory effects on trophoblast cells, identifying key miRNAs (miR-483-5p) and microbial taxa (Lactobacillales). These results indicate that exosomes and microbiota could play a role in EPL development by regulating trophoblast functions and inflammatory responses.