Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, United States
Luhan T Zhou
Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, United States
Christelle Guillermier
Department of Medicine, Aging Institute, University of Pittsburgh School of Medicine, Pittsburgh, United States; Department of Medicine, Division of Genetics, Brigham and Women’s Hospital, Boston, United States
Seby Edassery
Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States
Matthew L Steinhauser
Department of Medicine, Aging Institute, University of Pittsburgh School of Medicine, Pittsburgh, United States; Department of Medicine, Division of Genetics, Brigham and Women’s Hospital, Boston, United States
The mechanisms contributing to age-related deterioration of the female reproductive system are complex, however aberrant protein homeostasis is a major contributor. We elucidated exceptionally stable proteins, structures, and macromolecules that persist in mammalian ovaries and gametes across the reproductive lifespan. Ovaries exhibit localized structural and cell-type-specific enrichment of stable macromolecules in both the follicular and extrafollicular environments. Moreover, ovaries and oocytes both harbor a panel of exceptionally long-lived proteins, including cytoskeletal, mitochondrial, and oocyte-derived proteins. The exceptional persistence of these long-lived molecules suggest a critical role in lifelong maintenance and age-dependent deterioration of reproductive tissues.