Increased transcriptome variation and localised DNA methylation changes in oocytes from aged mice revealed by...

Area of Science:

• Reproductive biology
• Epigenetics
• Genomics

Background:

• Advancing maternal age progressively reduces fertility.
• Oocyte aging involves multiple factors, potentially including epigenetic alterations.
• Epigenetic changes in oocytes may affect early development or later offspring health.

Purpose of the Study:

• To investigate the impact of maternal aging on individual mouse oocyte transcriptome and DNA methylome.
• To identify age-related molecular changes in oocytes and their correlation with developmental competence.

Main Methods:

• Joint profiling of transcriptome and DNA methylome in individual oocytes from young and old mice.
• Analysis of gene expression patterns and CpG methylation.
• Identification of oocyte subpopulations based on transcriptomic profiles.

Main Results:

• Oocytes from aged females exhibit reduced transcriptome complexity and increased variance, forming distinct subpopulations.
• Reduced expression of maternal effect genes in a subset of aged oocytes indicates decreased developmental competence.
• Aged oocytes show reduced average CpG methylation, but the bimodal landscape is preserved; imprinted genes remain correctly methylated.
• Most age-related transcriptomic changes lack correlated methylation changes, suggesting post-transcriptional regulation.
• Differences in gene body methylation correlate with gene expression changes, indicating age-related transcriptional effects.

Conclusions:

• Maternal aging significantly alters mouse oocyte molecular profiles, affecting gene expression and methylation.
• Transcriptome heterogeneity in aged oocytes contributes to variable developmental competence.
• Age-related epigenetic modifications, particularly in gene bodies, influence gene expression and may impact offspring phenotypes.