The transition of maternal to zygotic gene expression regulation is critical for human pre-implantation embryo development. Recent years, single-cell RNA sequencing (scRNA-seq) had been applied to detect the factors that regulate human oocyte maturation and early embryo development. Here the evaluation of transcriptomes by scRNA-seq in the single blastomeres from the embryo collected from patients was performed. There were 20 blastomeres biopsied from 8-cell embryos of seven patients who received more than two ART cycles due to low embryo quality. Meanwhile, ten cells were collected from 8-cell embryos of four patients who received ART treatment due to male factor or tubal factor. The blastomeres were then evaluated using the previously established scRNA-seq method to determine the associations between the gene expression and its developmental competence. The total number of genes detected in 8-cell embryos that failed to form blastocyst including both maternal and zygotic mRNAs were reduced. There were 324 differently expressed genes detected among the 8-cell embryos including 65 genes that were significantly suppressed in the 8-cell embryos failed to form blastocyst. Further analyze found these 8-cell embryos arrested at cleavage stage due to the dysfunction of cell cycle, DNA transcription activity, histone methylation and cell division related genes such as SMCO-1, ZNF271P, ZNF679, ASF1b, BEX3, DPPA2 and ORC4. The alterations of gene expression detected in human 8-cell embryo are tightly associated with its developmental competence and could be used as targets to enhance embryo development or parameters to predict embryo’s development outcomes.

Lay Summary of Letter

Men and boys with cancer treated with chemotherapy are known to have reduced fertility following their treatment. This is because some chemotherapy drugs can damage the cells in the testicles that make sperm. This study found there is limited information available on the effect of one group of chemotherapy drugs, called taxanes, on testicular function and fertility. More studies are needed to aid clinicians in advising patients on how this taxane-based chemotherapy may affect their future fertility.