GSE173598
Dynamic mRNA Degradome Analyses Indicate a Role of Histone H3K4 Trimethylation in Association with Meiosis-coupled mRNA Decay in Oocyte Aging
A decrease in oocyte developmental potential is a major obstacle for successful pregnancy in women of advanced age. However, the age-related epigenetic modifications associated with dynamic transcriptome changes, particularly meiotic maturation-coupled mRNA clearance, have not been adequately characterized in human oocytes. This study demonstrate a decreased storage of transcripts encoding key factors regulating the maternal mRNA degradome in fully grown oocytes of women of advanced age. A similar defect in meiotic maturation-triggered mRNA clearance was also detected in aged mouse oocytes. Mechanistically, the epigenetic and cytoplasmic aspects of oocyte maturation are synchronized in both the normal development and aging processes. The level of histone H3K4 trimethylation (H3K4me3) was high in fully grown mouse and human oocytes derived from young females but decreased during aging due to the decreased expression of epigenetic factors responsible for H3K4me3 accumulation. Oocyte-specific knockout of the gene encoding CxxC-finger protein 1 (CXXC1), a DNA-binding subunit of SETD1 methyltransferase, caused ooplasm changes associated with accelerated aging and impaired maternal mRNA translation and degradation. These results suggest that a network of CXXC1-maintained H3K4me3, in association with mRNA decay competence, sets a timer for oocyte deterioration and plays a role in oocyte aging in both mouse and human oocytes. Overall design: A total of 44 samples were analyzed, including 24 human oocyte samples and 20 mouse oocyte samples. The human part included 8 individual biological cases, which were GV and MII stage oocytes from four differsnt age groups. Each case has 3 replicates. The mouse part included 7 individual biological cases, including GV and MII stage oocyte from young WT mouse (4 weeks),  GV and MII (with PB or without PB) stage oocyte from old WT mouse (14 months) and GV and MII stage oocyte from Cxxc1 conditional knock-out mouse.  Each case has 3 replicates, except that MII stage oocyte without PB from old WT mouse has only two replicates.