Search

Objective: A decrease in oocyte developmental potential occurs in most mammalian species, including humans, and is a major obstacle for successful pregnancy in women of advanced age. Transcriptome and translation changes related to spindle assembly and chromosome separation defects in aged oocytes have been described in prior studies. However, the mechanism underlying these abnormalities is unclear. The age-related epigenetic modifications associated with dynamic transcriptome changes, particularly meiotic maturation-coupled mRNA clearance, have not been adequately characterized in human oocytes. Methods: This study generated a genome-wide database of meiotic maturation-coupled mRNA degradation in both young and aged mouse and human oocytes. Results: The results of this study demonstrate a decreased storage of transcripts encoding key factors regulating the maternal mRNA degradome prior to the oocyte-to-zygotic transition (OZT) 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 but was more likely due to insufficient translation of mRNAs encoding these OZT factors. Mechanistically, the epigenetic and cytoplasmic aspects of oocyte maturation are synchronized in both the normal development and aging processes. For example, the level of H3K4me3 was high in fully grown mouse and human oocytes derived from young females but gradually decreased during aging due to the decreased expression of maternal epigenetic factors responsible for genomic H3K4me3 accumulation. Conclusion: Taken together, these results suggest that H3K4me3, in association with mRNA decay competence, sets a timer for oocyte deterioration and plays a leading role in oocyte aging in both mouse and human oocytes. [ABSTRACT FROM AUTHOR]