Aneuploidy-driven gene expression profiling in human blastocysts: insights from RNA-Seq analysis

Preimplantation aneuploidy in humans is one of the primary causes of implantation failure and embryo miscarriage. This study was conducted to gain insight into gene expression changes that may result from aneuploidy in blastocysts through RNA-Seq analysis.

The surplus embryos of preimplantation genetic testing for aneuploidy (PGT-A) candidate couples with normal karyotype and maternal age < 38 were collected following identical ovarian stimulation protocol. The embryos were selected based on trophectoderm biopsy and array comparative genomic hybridization in three groups: normal group, small chromosomes aneuploidy group (SCA), including single aneuploidy for small chromosomes 16, 20, 21, 22, and other chromosomes aneuploidy group (OCA), including single aneuploidy for other chromosomes.

Principal component analysis revealed overall differentiation of transcriptome of the groups, confirming embryo classification. The Gene Ontology indicated that transcription, ubiquitination, autophagy, and DNA repair pathways were upregulated in aneuploid embryos. The overexpression of five genes, UBE2E2 and VPS4A, BUB1B, CDCA8, and COX14 was confirmed by quantitative real-time PCR. Additionally, overexpression was observed in translation and protein synthesis pathways in aneuploid embryos. Mitochondrial pathway upregulation was notable in both SCA and OCA groups, while the apoptosis pathway was overexpressed only in the OCA group. Only cellular lipid synthesis pathway differed between SCA and OCA, the two aneuploid groups.

This study highlights the impact of aneuploidy on the gene expression in blastocysts independent of aneuploidy type and paves the way for understanding the molecular mechanisms underlying the generation of aneuploidy.