Landscape of extrachromosomal circular DNAs and transcriptome in fetal growth restriction with trisomy 16 [mRNA]

ABSTRACT: Rare autosomal trisomies (RAT) are a leading cause of early embryonic growth restriction and spontaneous abortion in humans. Non-invasive prenatal testing (NIPS) has demonstrated high accuracy and specificity for common autosomal trisomies (21, 18, and 13), but effective biomarkers for RAT are still lacking. Previous studies have detected fetal eccDNA in maternal plasma samples, and its biological stability and unique molecular structural characteristics have shown great potential for the development of novel biomarkers for NIPS. Given the genome-wide nature of the NIPS, eccDNA-related features are inevitably covered. However, our current understanding of the characteristics of RAT-eccDNA is limited, resulting in slow progress in the development of risk assessment systems for adverse pregnancy outcomes based on eccDNA. In this study, we collected chorionic villus samples from three pregnant women who underwent dilation and curettage due to early embryonic arrest caused by trisomy 16, as well as from three cases of embryonic arrest caused by chromosomally normal embryos. Combined with Circle-Seq and mRNA-Seq, the eccDNA and transcriptome characteristics of trisomy 16 were described in detail in this study. The results showed that Trisomy 16 was associated with a distinct eccDNA signature characterized by altered chromosomal distribution, relative depletion of 200 bp fragments, and enrichment of 400 bp eccDNAs. Concurrent transcriptome analysis revealed 481 differentially expressed genes; upregulated genes were concentrated in extracellular matrix and ion channel functions, whereas downregulated genes were enriched in immune surveillance pathways, including T cell differentiation and chemokine signaling. These findings provide the first comprehensive characterization of eccDNA landscapes in trisomy 16, establish a molecular framework for understanding RAT-induced placental pathology, and support the theoretical feasibility of incorporating eccDNA analysis into NIPS platforms to improve non-invasive detection and genetic counseling for rare chromosomal trisomy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE339289 | GEO | 2026/09/09

REPOSITORIES: GEO