Transcriptomic profiles of human parthenogenotes: contribution of the maternal genome across the early embryo...

To study the maternal contribution to early human embryogenesis by describing the transcriptional dynamics and regulatory roles of maternal effect genes (MEGs) and transcription factors (TFs) throughout the first four cell cycles. This will be achieved using parthenogenotes, such as the human uniparental bioconstruct model.

Descriptive observational study based on single-cell transcriptomic analysis.

A total of 19 single human parthenocytes were derived from six parthenogenotes at the first (n = 2), third (n = 2), and fourth (n = 2) cell cycles.

Transcriptomic changes occurring during early embryonic development in the absence of paternal genomic input.

Transcript abundance of MEGs, expression levels of key TFs, number and identity of differentially expressed genes (DEGs), pathway enrichment associated with DEGs, transcriptional complexity, temporal patterns of MEG transcript decay and persistence and timing of embryonic genome activation (EGA).

Transcriptomic analysis revealed progressive increases in transcriptional complexity, with major shifts between the third and fourth cell cycles coinciding with EGA. A total of 212 and 1,515 DEGs were identified in the third and fourth cycles, respectively (fold change ≥|2| vs. first cycle), predominantly involved in ribonucleic acid biosynthesis and cell proliferation pathways. Principal component and hierarchical clustering analyses showed distinct transcriptomic profiles by cell cycle and oocyte origin. Key TFs (DUXA, DUX4, Elk-1, E2F-1, Sp1) were implicated in cell cycle regulation. The MEG analysis revealed decay of transcripts associated with messenger ribonucleic acid clearance, alongside sustained expression of MEGs linked to cell cycle progression and spindle assembly, suggesting a nonrandom, structured maternal regulatory program.

This study provides the first comprehensive single-cell transcriptomic characterization of early human parthenogenotes, suggesting a structured, genome-driven maternal program that governs early embryonic development in the absence of paternal input. The identification of key TFs and MEG signature highlights the pivotal regulatory role of the maternal genome before EGA and may inform strategies to improve outcomes in assisted reproductive technologies.