Transcriptomic Profiling Reveals Biphasic Regulatory Instability and Late-Stage Proteostatic Decline in Aging Mouse...

Area of Science:

• Reproductive Biology
• Molecular Biology
• Aging Research

Background:

• Maternal aging negatively impacts oocyte quality and fertility.
• The molecular mechanisms underlying oocyte aging across the reproductive lifespan are not fully understood.

Purpose of the Study:

• To define the transcriptomic landscape of mouse oocytes at different reproductive stages.
• To elucidate the molecular trajectory of oocyte aging.

Main Methods:

• Transcriptomic profiling of mouse germinal vesicle (GV) oocytes from young, middle-aged, and old mice.
• Bioinformatic analysis, including differential gene expression (DEG) analysis and transcription factor binding site (TFBS) analysis.

Main Results:

• Oocyte aging follows a biphasic, nonlinear trajectory.
• The transition from young to middle age showed significant transcriptional destabilization (1197 DEGs) affecting metabolic and signaling networks, potentially driven by epigenetic modifications rather than transcription factor depletion.
• The transition from middle to old age was characterized by mitochondrial dysfunction and proteostatic stress, indicating systemic collapse.

Conclusions:

• Oocyte aging is a biphasic process involving compensatory resistance followed by systemic collapse.
• Midlife represents a critical inflection point for regulatory remodeling in oocytes.
• These findings offer a molecular basis for developing strategies to combat age-related infertility.