Human blastocysts of normal and abnormal karyotypes display distinct transcriptome profiles

Area of Science:

• Developmental Biology
• Genetics
• Reproductive Medicine

Background:

• Human blastocyst transcriptome analysis offers insights into early embryonic development and viability.
• Comparing gene expression in normal versus aneuploid embryos can elucidate pathways of normal and aberrant fetal development.
• Identifying specific transcripts related to chromosome copy number variations may lead to non-invasive embryo selection methods for IVF.

Purpose of the Study:

• To comprehensively delineate the transcriptome of human blastocysts with varying karyotypes.
• To identify common gene expression patterns in normal and aneuploid embryos.
• To discover potential biomarkers for non-invasive assessment of embryo viability.

Main Methods:

• RNA sequencing (RNA-seq) was used to analyze the transcriptomes of 71 human blastocysts.
• Embryos analyzed included those with normal karyotypes, autosomal aneuploidies (trisomies and monosomies), and sex chromosome abnormalities.
• Transcriptome profiles were compared between normal and aneuploid embryos.

Main Results:

• A core set of over 3,000 genes is expressed in all normal human blastocysts, involved in cell division and metabolism.
• Aneuploid embryos exhibited significant gene dysregulation compared to normal embryos, with some showing over 100-fold expression differences.
• Sex chromosome aneuploidies (XO, XXX) had transcriptomes more similar to normal embryos than autosomal aneuploidies.
• A common set of deregulated genes was identified in the majority of both trisomic and monosomic embryos.

Conclusions:

• This study provides the first comprehensive transcriptome map of human pre-implantation embryos with karyotypic abnormalities.
• The findings contribute to understanding developmental abnormalities and may inform the development of novel pre-implantation genetic screening (PGS) techniques.
• Identifying unique gene expression signatures can aid in developing non-invasive methods for selecting the most viable embryos for IVF transfer.