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Zaffagnini, G.

Publications and source records attributed to Zaffagnini, G..

3 recordsLinked to original sources

The proteostatic landscape of healthy human oocytes

Oocytes are among the longest-lived cells in the body. Recent studies on mouse oocytes highlight unique adaptations in protein homeostasis (proteostasis) within these cells. However, the mechanisms of proteostasis in human oocytes remain virtually unstudied. We present the first large-scale study of proteostatic activity in human oocytes using over 100 freshly-donated oocytes from 21 healthy women aged 19-34. We analyzed the activity and distribution of lysosomes, proteasomes, and mitochondria in both immature and mature oocytes. In contrast to mice, where degradative activity increases during oocyte maturation, human oocytes exhibit nearly 2-fold lower degradative activity than surrounding somatic cells, which decreases further as oocytes mature. Oocyte maturation is also coupled with a decrease in mitochondrial membrane potential. We propose that reduced organelle activity preserves cellular components during the prolonged maturation in human oocytes. Our findings highlight the need to directly investigate human oocyte biology to address challenges in female fertility.

cell biology↗

A novel RNP compartment boosts translation in growing mouse oocytes to avoid cytoplasm dilution

Mammalian oocytes undergo a long growth phase in the ovary, during which transcriptional levels gradually decrease. Growing oocytes must therefore accumulate maternal stores and regulate their translation to achieve successful divisions and early embryo development. Using immunofluorescence, mass spectrometry and electron microscopy, we identified a novel and transient compartment, the Zollo Body, in late growing mouse oocytes, constituted of RNPs and organelles. Morphologically, this structure resembles the Balbiani body found in most vertebrate species but it stains positively for nascent translation and active phospho-mTOR. RNAseq analysis and dry mass measurements of growing oocytes with or without this compartment further support its key role in boosting translation, allowing growing oocytes to avoid cytoplasmic dilution despite their rapid size increase, ultimately ensuring their developmental potential.

cell biology↗

Mouse oocytes do not contain a conventional Balbiani body

Oocytes spend the majority of their lifetime in a primordial, dormant state. Unlike many somatic cell types and mature oocytes, the cellular and molecular biology of primordial oocytes is largely unexplored. Yet, studying their cellular biology is necessary to understand the mechanisms through which oocytes maintain cellular fitness for decades, and why they eventually fail with age. A hallmark of primordial oocytes in many species is the Balbiani body, a non-membrane bound compartment that contains the majority of mitochondria in the oocyte cytoplasm. The Balbiani body has been proposed to be essential for maintaining mitochondria in a healthy state during long-lasting dormancy, however, the architecture and function of the mammalian Balbiani body remains unknown. Here, we develop enabling methods for live-imaging based comparative characterization of Xenopus, mouse and human primordial oocytes. We show that primordial oocytes in all three vertebrate species contain active mitochondria, Golgi apparatus and lysosomes. We further demonstrate that human and Xenopus oocytes have a Balbiani body characterized by a dense accumulation of mitochondria in their cytoplasm. However, despite previous reports, we did not find a Balbiani body in mouse oocytes. Instead, we demonstrate what was previously used as a marker for the Balbiani body in mouse primordial oocytes is in fact a ring-shaped Golgi apparatus that is not functionally associated with oocyte dormancy. Our work provides the first insights into the organisation of the cytoplasm in mammalian primordial oocytes, and clarifies relative advantages and limitations of choosing different model organisms for studying oocyte dormancy.

cell biology↗