The proteostatic landscape of healthy human oocytes.

The discovery we made in this paper is that human oocytes exhibit remarkably low proteasomal, lysosomal, and mitochondrial activity, which declines even further as they mature into fertilizable eggs. This study, based on over 100 healthy human oocytes from more than 20 young donors, provides a foundational reference for research on protein homeostasis (proteostasis) in reproductive aging and infertility.It was motivated by the following question: While our previous work in mice revealed how oocytes regulate proteostasis through temporally coordinated degradation pathways, the regulation of proteostasis in human oocytes remained unknown. Given the long lifespan and unique developmental timeline of human oocytes, we aimed to determine how key organelles—lysosomes, proteasomes, and mitochondria—are functionally and spatially regulated. Using oocytes donated by young, healthy women, this study uncovered human-specific strategies that may be critical for preserving oocyte quality and fertility over time.