ESPEYB21 14. The Year in Science and Medicine Basic Biology and Molecular Mechanisms (5 abstracts)
14.1. The maintenance of oocytes in the mammalian ovary involves extreme protein longevity
Katarina Harasimov , Rebecca L. Gorry , Luisa M. Welp , Sarah Mae Penir , Yehor Horokhovskyi , Shiya Cheng , Katsuyoshi Takaoka , Alexandra Stützer , Ann-Sophie Frombach , Ana Lisa Taylor Tavares , Monika Raabe , Sara Haag , Debojit Saha , Katharina Grewe , Vera Schipper , Silvio O. Rizzoli , Henning Urlaub , Juliane Liepe & Melina Schuh
Nature Cell Biology, Volume 26, July 2024: 1124–1138. doi: 10.1038/s41556-024-01442-7
Brief Summary:The female ovary is essential for reproduction. Oocytes are stored in it for more than a year in mice, and for more than four decades in humans. This study investigated proteostasis in oocytes and ovaries of mice by combining quantitative mass spectrometry (MS), pulse–chase labelling, single-cell RNA-seq and nanoscale secondary ion MS (NanoSIMS). They found extraordinary stability of hundreds of proteins. Long-lived proteins were enriched in diverse cellular components (e.g., mitochondria, ribosome, spliceosome, proteasome, chromatin, kinetochore and cytoskeleton) and functions (e.g., metabolism, chaperones, DNA repair and antioxidants). Long-lived somatic cells, including granulosa and stromal cells, as well as individual cells in the theca layer were also identified. The demise of oocytes and the ovary with aging was paralleled by the eventual loss of highly stable proteins.
The ovarian follicle pool plays an important role in female fertility, but insight into its formation, maintenance and decay is missing. Primary or premature ovarian failure as seen with Turner syndrome is a frequent disorder that disables fertility. Basic studies to understand how the ovarian follicle pool is preserved, and what proteins and pathways are involved, are key to understand its normal biology and related diseases. This study provides an enormous amount of data including an atlas of the abundance of ovarian proteins and their changes throughout development. It is fascinating to learn that the ovaries have a >10-fold higher fraction of extremely long-lived proteins than other post-mitotic tissues. This guarantees the maintenance and intactness of oocytes over a longer time period. However, with aging even ovarian long-lived proteins are lost. Their identification may help in uncovering the principles involved in resetting the aging clock and inform new therapeutic strategies to delay age-related diseases.
Another interesting article related to the topic informs SF-1 as a key regulator of the formation of the ovarian reserve.
Related literature: Exceptional longevity of mammalian ovarian and oocyte macromolecules throughout the reproductive lifespan
Ewa K Bomba-Warczak, Karen M Velez, Luhan T Zhou, Christelle Guillermier, Seby Edassery, Matthew L Steinhauser, Jeffrey N Savas, Francesca Elizabeth Duncan bioRxiv [Preprint]. 2024 Jul 5:2023. doi: 10.1101/2023.10.18.562852
Steroidogenic factor 1 (SF-1; Nr5a1) regulates the formation of the ovarian reserve.
Camilla H. K. Hughes, Olivia E. Smith, Marie-Charlotte Meinsohn, Mylène Brunelle, Nicolas Gévry, Bruce D. Murphy PNAS 2023, Vol. 120 No. 32, e2220849120. doi: 10.1073/pnas.2220849120
Volume 21
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ESPE Yearbook of Paediatric Endocrinology
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