Age‐associated dysregulation of protein metabolism in the mammalian oocyte
| العنوان: | Age‐associated dysregulation of protein metabolism in the mammalian oocyte |
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| المؤلفون: | Francesca E. Duncan, Barbara Fegley, Susmita Jasti, Jennifer L. Gerton, John M. Kelsh, Ariel Paulson |
| المصدر: | Aging Cell |
| بيانات النشر: | John Wiley and Sons Inc., 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Aging, Nucleolus, Biology, Oogenesis, 03 medical and health sciences, folliculogenesis, Protein biosynthesis, medicine, Animals, nucleolus, Transcription factor, Fibrillarin, proteostasis, Reproduction, Cell Biology, Meiotic chromosome segregation, Original Articles, Oocyte, Cell biology, 030104 developmental biology, Proteostasis, medicine.anatomical_structure, reproductive aging, ribosome, Oocytes, Original Article, Female |
| الوصف: | Summary Reproductive aging is characterized by a marked decline in oocyte quality that contributes to infertility, miscarriages, and birth defects. This decline is multifactorial, and the underlying mechanisms are under active investigation. Here, we performed RNA‐Seq on individual growing follicles from reproductively young and old mice to identify age‐dependent functions in oocytes. This unbiased approach revealed genes involved in cellular processes known to change with age, including mitochondrial function and meiotic chromosome segregation, but also uncovered previously unappreciated categories of genes related to proteostasis and organelles required for protein metabolism. We further validated our RNA‐Seq data by comparing nucleolar structure and function in oocytes from reproductively young and old mice, as this organelle is central for protein production. We examined key nucleolar markers, including upstream binding transcription factor (UBTF), an RNA polymerase I cofactor, and fibrillarin, an rRNA methyltransferase. In oocytes from mice of advanced reproductive age, UBTF was primarily expressed in giant fibrillar centers (GFCs), structures associated with high levels of rDNA transcription, and fibrillarin expression was increased ~2‐fold. At the ultrastructural level, oocyte nucleoli from reproductively old mice had correspondingly more prominent fibrillar centers and dense fibrillar centers relative to young controls and more ribosomes were found in the cytoplasm. Taken together, our findings are significant because the growing oocyte is one of the most translationally active cells in the body and must accumulate high‐quality maternally derived proteins to support subsequent embryo development. Thus, perturbations in protein metabolism are likely to have a profound impact on gamete health. |
| اللغة: | English |
| تدمد: | 1474-9726 1474-9718 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c227b77972dfaf4201627be271fadc91 http://europepmc.org/articles/PMC5676066 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c227b77972dfaf4201627be271fadc91 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14749726 14749718 |
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