CNOT3 resists ovarian aging by accelerating oocyte maturation and promoting ESCs differentiation

Area of Science:

• Reproductive Biology
• Cellular and Molecular Medicine

Background:

• Ovarian aging (OA) reduces oocyte quality and quantity, posing a challenge in reproductive medicine.
• Therapeutic targets and methods for OA are not well-defined.
• Embryonic stem cells (ESCs) show potential in resisting OA, but the mechanisms are unclear.

Purpose of the Study:

• To investigate the role of CNOT3 in ovarian aging (OA) and oocyte maturation.
• To explore the therapeutic potential of ESCs in combating OA.

Main Methods:

• Quantitative real-time PCR (RT-qPCR) and Western blotting to assess CNOT3 expression.
• RNA sequencing (RNA-seq) to analyze gene expression changes.
• Micro-injection and *in vitro* cell differentiation assays to evaluate CNOT3 function and ESC differentiation into primordial germ cell-like cells (PGCLCs).
• ESC transplantation in mice to assess therapeutic effects on OA.

Main Results:

• CNOT3 expression decreases in aging ovaries of pigs and mice.
• CNOT3 accelerates oocyte maturation and resists OA.
• CNOT3 upregulates pluripotency genes in mouse ESCs and promotes their differentiation into PGCLCs.
• ESC transplantation ameliorates OA in mice, an effect reversed by CNOT3 knockdown.

Conclusions:

• CNOT3 is a critical regulator that counteracts OA and enhances the therapeutic efficacy of ESCs.
• These findings provide valuable information for developing improved therapeutic strategies for OA.