After fertilization in mammals, the genome of the newly formed embryo is first transcriptionally inactive.
Development is then strictly dependent on the maternally inherited RNA and proteins present in the oocyte that were accumulated before ovulation during oocyte growth and maturation. The onset of transcription specific to the embryo, referred to as “embryonic genome activation (EGA)”, is initiated later during development at various preimplantation stages according to species.
Transcriptional activity can be underlined thanks to several approaches such as precursor’s incorporation in newly synthesized RNA and expression of reporter genes.
These studies show that EGA is established in two phases: a “minor” one, first with reduced transcriptional activity and that does not require any specific transcription factor; second, a “major” phase with rapidly increasing transcription. Upon major activation, newly synthesized RNA/proteins are essential for further embryonic development.
EGA is dependent on the availability and activity of the basal transcriptional machinery components but also on the structural modifications of the nuclei after fertilization. Indeed, during the first embryonic cycles, the maternal and paternal genome undergoes intense chromatin remodeling that could be a key regulator of embryonic transcription.
In human embryos, the initiation of transcription (embryonic genome activation [EGA]) occurs by the eight-cell stage, but its exact timing and profile are unclear. To address this, we profiled gene expression at depth in human metaphase II oocytes and bipronuclear (2PN) one-cell embryos.
High-resolution single-cell RNA sequencing revealed previously inaccessible oocyte-to-embryo gene expression changes. This confirmed transcript depletion following fertilization (maternal RNA degradation) but also uncovered low-magnitude upregulation of hundreds of spliced transcripts.
Gene expression analysis predicted embryonic processes including cell-cycle progression and chromosome maintenance as well as transcriptional activators that included cancer-associated gene regulators. Transcription was disrupted in abnormal monopronuclear (1PN) and tripronuclear (3PN) one-cell embryos.
These findings indicate that human embryonic transcription initiates at the one-cell stage, sooner than previously thought.
The pattern of gene upregulation promises to illuminate processes involved at the onset of human development, with implications for epigenetic inheritance, stem-cell-derived embryos, and cancer.
