Age-associated dysregulation of protein metabolism in the mammalian oocyte

Francesca E. Duncan*, Susmita Jasti, Ariel Paulson, John M. Kelsh, Barbara Fegley, Jennifer L. Gerton

*Corresponding author for this work

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1381-1393
Number of pages13
JournalAging Cell
Volume16
Issue number6
DOIs
StatePublished - Dec 2017

Keywords

  • folliculogenesis
  • nucleolus
  • oogenesis
  • proteostasis
  • reproductive aging
  • ribosome

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Fingerprint Dive into the research topics of 'Age-associated dysregulation of protein metabolism in the mammalian oocyte'. Together they form a unique fingerprint.

  • Cite this

    Duncan, F. E., Jasti, S., Paulson, A., Kelsh, J. M., Fegley, B., & Gerton, J. L. (2017). Age-associated dysregulation of protein metabolism in the mammalian oocyte. Aging Cell, 16(6), 1381-1393. https://doi.org/10.1111/acel.12676