Transcriptomic behavior of genes associated with chromosome 21 aneuploidies in early embryo development

Transcriptomics of chromosome 21 aneuploidies in blastocyst reveal fewer changes than expected in trisomy 21, in line with morphological criteria suggesting a dosage-compensation mechanism.

Volume 111, Issue 5, Pages 991–1001.e2


Imma Sanchez-Ribas, M.D., Patricia Diaz-Gimeno, Ph.D., Patricia Sebastián-León, Ph.D., Amparo Mercader, Ph.D., Alicia Quiñonero, B.Sc., Agustín Ballesteros, M.D., Antonio Pellicer, M.D., Francisco Domínguez, Ph.D.



To analyze how chromosome 21 (HSA21) ploidy affects global gene expression of early human blastocysts.


Prospective study.


University-affiliated in vitro fertilization clinic.


A total of 26 high-quality donated embryos from in vitro fertilization (IVF) patients: trisomy 21 (n = 8), monosomy 21 (n = 10), and euploid (n = 8) blastocysts.



Main Outcome Measure(s)

Blastocyst transcriptome changes and its associated functions.


Trisomy 21, monosomy 21, and euploid blastocysts were classified by comparative genomic hybridization. The global transcriptome of whole blastocysts was analyzed with small cell number RNA sequencing, and they were compared to understand the gene expression behavior at early development and its implications for embryo implantation. We identified 1,232 differentially expressed genes (false discovery rate <0.05) in monosomy 21 compared with euploid blastocysts associated with dysregulated functions in embryo development as the Rap1 signaling pathway. Curiously, Down syndrome in early development revealed fewer transcriptomic changes than expected. In addition, Down syndrome gene expression in neonates, children, and adults revealed that the number of deregulated genes increases across life stages from blastocysts to adults, suggesting a potential dosage-compensation mechanism for human chromosome 21.


At the transcriptomic level, early development in Down syndrome is mainly dosage compensated. However, monosomy 21 is strongly transcriptionally affected because early development involving main functions is associated with embryo implantation.

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