Evolutionarily divergent transcriptomic programs in ovarian folliculogenesis across mice, monkeys and humans

Area of Science:

• Reproductive Biology
• Developmental Biology
• Genomics

Background:

• Understanding human ovarian folliculogenesis is crucial for reproductive medicine.
• Oocyte and granulosa cell (GC) interactions are key to follicle development.
• Comparative transcriptomic analysis across species can reveal conserved and divergent mechanisms.

Purpose of the Study:

• To investigate and compare transcriptomic dynamics in oocytes and GCs during folliculogenesis across mice, monkeys, and humans.
• To identify species-specific differences and conserved pathways in ovarian follicle development.
• To establish and evaluate in vitro culture systems for human and monkey preantral follicle development.

Main Methods:

• Single-cell RNA sequencing of oocytes and GCs at various folliculogenesis stages.
• Comparative transcriptomic analysis to identify highly variable genes (HVGs) and conserved/divergent pathways.
• Development and assessment of in vitro culture systems for primate follicle development.

Main Results:

• Monkey and human oocytes exhibit minimal transcriptomic changes until the secondary follicle stage, unlike mice.
• Most HVGs in oocytes showed monotonic regulation with limited cross-species overlap.
• GC transcriptomic trajectories and intercellular communication pathways (e.g., signaling, gap junctions) were species-specific.
• Conserved mechanisms include X-chromosome dosage compensation and transposon repression.
• In vitro culture supported follicle development but revealed aberrant GC profiles despite normal oocyte maturation.

Conclusions:

• Ovarian folliculogenesis involves significant species-specific transcriptomic and intercellular communication differences.
• This comparative framework aids understanding of human ovarian development and in vitro reconstruction.
• Aberrant GC profiles in vitro highlight challenges in recapitulating native ovarian microenvironments.