Elvan Böke

Mammalian oocytes undergo an extended growth phase, during which transcription gradually declines. To sustain meiotic divisions and early embryonic development, growing oocytes must accumulate maternal stores and tightly regulate translation. Using immunofluorescence, mass spectrometry, electron microscopy, RNA sequencing, and live ex vivo ovarian tissue–slice imaging, we identified a transient ribonucleoprotein-organelle compartment in growing mouse oocytes, which we named the Zollo body. Although it resembles the Balbiani body observed in nongrowing oocytes of many vertebrate species, the Zollo body arises during growth and shows nascent translation and phospho-mTOR enrichment. Pharmacological dissolution of the Zollo body arrests follicle and oocyte growth in cultured ovarian tissue slices. Thus, the Zollo body is a transient, translation-associated compartment required for normal follicle and oocyte growth.

Oocytes, female germ cells that develop into eggs, are among the longest-lived cells in the animal 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 years. We analysed the activity and distribution of lysosomes, proteasomes, and mitochondria in both immature and mature oocytes. Notably, human oocytes exhibit nearly twofold lower proteolytic activity than surrounding somatic cells, with further decreases as oocytes mature. Oocyte maturation is also coupled with lysosomal exocytosis and a decrease in mitochondrial membrane potential. We propose that reduced organelle activity preserves key cellular components critical for early embryonic development during the prolonged maturation of human oocytes. Our findings highlight the distinctive biology of human oocytes and the need to investigate human-specific reproductive biology to address challenges in female fertility.

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.

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.

The Balbiani body (Bb), which was discovered about 170 years ago, is a membraneless organelle in the oocyte in most species. In organisms like Xenopus and Zebrafish, Bb accumulates mitochondria, endoplasmic reticulum (ER), and germline determinants and regulates the proper localization of germline determinants. The Bb forms around the centrosome in the oocyte during early oogenesis. The mechanism behind its assembly has gained attention only very recently. Here, we report that overexpression of the germ plasm matrix protein Xvelo leads to the formation of a ‘Bb-like’ structure in somatic cells. The ‘Bb-like’ structure assembles around the centrosome and selectively recruits mitochondria, ER, and germline determinants. Taking advantage of this system, we investigated the roles of centrosome components on the assembly of Xvelo. Our results reveal that multiple components of the centrosome, including Sas6, Cenexin, and DZIP1, interact with Xvelo and promote its assembly, with Sas6 exhibiting the most prominent activity. Importantly, knocking down Sas6, Cenexin, and DZIP1 individually or in combination resulted in reduced Xvelo aggregates. Taken together, our work suggests that the centrosome may function as a nucleation center to promote the initiation of Xvelo assembly, resulting in the formation of the Bb around the centrosome.