Mammalian oocytes store mRNAs in a mitochondria-associated membraneless compartment

Cheng, Shiya; Altmeppen, Gerrit; So, Chi‐Chiu; Welp, Luisa M.; Penir, Sarah Mae U.; Ruhwedel, Torben; Menelaou, Katerina; Harasimov, Katarina; Stützer, Alexandra; Blayney, Martyn; Elder, Kay; Möbius, Wiebke; Urlaub, Henning; Schuh, Melina

doi:10.1126/science.abq4835

Cited by 73 publications

(58 citation statements)

References 106 publications

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“…Oocytes lack both an interphase and an S-phase between Meiosis I and II, and they are transcriptionally silent until zygotic genome activation in embryos at the 2-cell stage in mice and 8-cell stage in humans. A recent study reports a mitochondria-dependent mode of mRNA storage in mammalian oocytes in a phase-separated, membraneless region called MARDO important for regulating translation and, consequently, proper embryo development 39 . The common theme of oocytes using membraneless organelles to control RNA storage and localization, and spindle quality 22 points to a mechanism by which cells overcome the challenges of having a large cytoplasm.…”

Section: Resultsmentioning

confidence: 99%

A meiotic midbody structure in mouse oocytes acts as a barrier for nascent translation to ensure developmental competence

Jung

Londoño-Vásquez

Park

et al. 2022

Preprint

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Successful embryo development is dependent upon maternally deposited components. During egg formation, developmental competence is acquired through regulated translation of maternal mRNA stores. In addition, egg precursors undergo two rounds of chromosome segregation, each coupled to an asymmetric cytokinesis that produces two non-functional polar bodies. In somatic cells, cytokinesis produces two daughter cells and one midbody remnant (MBR), a signaling organelle assembled from the midbody (MB), which first appears in Telophase. MBs contain transcription and translation factors, and epigenetic modifiers. Once MBs mature to MBRs by abscission, they can be subsequently phagocytosed by another cell and influence cellular function or fate. Although the significance of MBs is elucidated in several cell types like neurons, cancer cells and stem cells, the presence and function of MBs in gametes and their roles in reproductive fitness are unknown. Here, we examined the formation and regulation of meiotic midbodies (mMB) in mouse oocytes. We find that although mouse oocyte mMBs contain analogous structures to somatic MBs, they also have a unique cap-like structure composed of the centralspindlin complex, and that cap formation depends upon an asymmetric microtubule abundance in the egg compared to the polar body. Furthermore, our results show that mMBs are translationally active ribonucleoprotein granules, supported by detection of ribosomes, polyadenylated mRNAs and nascent translation. Finally, by pharmacological and laser ablation-based approaches, we demonstrate that the mMB cap is a barrier to prevent translated products from leaving the egg and escaping into the polar body. Crucially, this barrier is critical for successful early embryonic development. Here, we document an evolutionary adaptation to the highly conserved process of cytokinesis in mouse oocytes and describe a new structure and new mechanism by which egg quality and embryonic developmental competence are regulated.

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Section: Resultsmentioning

confidence: 99%

A meiotic midbody structure in mouse oocytes acts as a barrier for nascent translation to ensure developmental competence

Jung

Londoño-Vásquez

Park

et al. 2022

Preprint

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“…In transcriptionally-silent oocytes, the cytoplasm stores maternal mRNAs and ensures spatial and temporal control over the translation and degradation of transcripts synthesized during oogenesis (51). A recent study showed that mammalian oocytes, including humans, dock their maternal mRNA in mitochondria-associated membrane-less domains (52). Anomalous organelle distribution seen in aberrant oocytes is likely to compromise the availability of mRNA and, thus, the efficiency of protein synthesis and post-translation modifications.…”

Section: Discussionmentioning

confidence: 99%

The ultrastructural nature of human oocytes’ cytoplasmatic abnormalities and the role of cytoskeleton dysfunction

Tatíčková

Trebichalská

Kyjovská³

et al. 2023

Preprint

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Egg quality is a limiting factor of female fertility and assisted reproductive technology (ART) success. Oocytes recovered from hyperstimulated ovaries often display morphological anomalies suspected to compromise their fertilization and developmental potential. Knowledge of (ab)normal oocyte’s intracellular organization is vital to establish reliable criteria for morphological evaluation of oocytes intended for in vitro fertilization (IVF). Here, we investigated the fine morphology of 22 dysmorphic IVF oocytes exhibiting different types of cytoplasmic irregularities, namely (1) refractile bodies, (2) centrally-located cytoplasmic granularity (CLCG), (3) smooth endoplasmic reticulum (SER) disc, and (4) vacuoles. Transmission electron microscopy (TEM) revealed the structural basis of these aberrations and indicated that the underlying cause of two of the studied morphotypes was inordinate organelle clustering. To address the mechanism required for accurate organelle positioning, we used cytoskeleton-targeting chemical compounds and performed a series of inhibition experiments involving a total of 133 human oocytes maturing in vitro. Fluorescence and electron microscopy showed that disruption of actin, not microtubules, led to the aggregation of subcellular structures resembling the morphological pattern seen in abnormal oocytes. These results imply that actin serves as a regulator of organelle distribution during human oocyte maturation. The ultrastructural analogy between dysmorphic eggs retrieved in IVF cycles and oocytes, in which actin network integrity was perturbed, suggests that dysfunction of the actin cytoskeleton might be implicated in generating common cytoplasmic aberrations. Knowledge of human oocytes’ inner workings and the origin of morphological abnormalities is a step forward to more objective egg quality assessment in clinical practice.SUMMARY SENTENCEUltrastructural analysis of eggs exhibiting cytoplasmic abnormalities combined with inhibition experiments indicates that dysfunction of the actin network might be involved in the development of oocyte dysmorphisms.

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“…Another study revealed a membraneless compartment storing mRNAs around mitochondria in the germinal vesicle oocyte (Cheng et al, 2022). Combining these evidence, it's likely that RNAs, including those transported from CCs, would aggregate in this compartment if the biosynthesis load is not high.…”

Section: Effects On Oocytes: Meiosismentioning

confidence: 98%

“…Cutting off this RNA transmission can cause impaired oocyte development and a significant reduction in maturation rate, which would confirm our hypothesis. Another study revealed a membraneless compartment storing mRNAs around mitochondria in the germinal vesicle oocyte ( Cheng et al, 2022 ). Combining these evidence, it’s likely that RNAs, including those transported from CCs, would aggregate in this compartment if the biosynthesis load is not high.…”

Section: Functions Of Intercellular Communication In Cocmentioning

confidence: 99%

Intercellular communication in the cumulus–oocyte complex during folliculogenesis: A review

Xie

Liu

2023

Front. Cell Dev. Biol.

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During folliculogenesis, the oocyte and surrounding cumulus cells form an ensemble called the cumulus-oocyte complex (COC). Due to their interdependence, research on the COC has been a hot issue in the past few decades. A growing body of literature has revealed that intercellular communication is critical in determining oocyte quality and ovulation. This review provides an update on the current knowledge of COC intercellular communication, morphology, and functions. Transzonal projections (TZPs) and gap junctions are the most described structures of the COC. They provide basic metabolic and nutrient support, and abundant molecules for signaling pathways and regulations. Oocyte-secreted factors (OSFs) such as growth differentiation factor 9 and bone morphogenetic protein 15 have been linked with follicular homeostasis, suggesting that the communications are bidirectional. Using advanced techniques, new evidence has highlighted the existence of other structures that participate in intercellular communication. Extracellular vesicles can carry transcripts and signaling molecules. Microvilli on the oocyte can induce the formation of TZPs and secrete OSFs. Cell membrane fusion between the oocyte and cumulus cells can lead to sharing of cytoplasm, in a way making the COC a true whole. These findings give us new insights into related reproductive diseases like polycystic ovary syndrome and primary ovarian insufficiency and how to improve the outcomes of assisted reproduction.

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Mammalian oocytes store mRNAs in a mitochondria-associated membraneless compartment

Cited by 73 publications

References 106 publications

A meiotic midbody structure in mouse oocytes acts as a barrier for nascent translation to ensure developmental competence

A meiotic midbody structure in mouse oocytes acts as a barrier for nascent translation to ensure developmental competence

The ultrastructural nature of human oocytes’ cytoplasmatic abnormalities and the role of cytoskeleton dysfunction

Intercellular communication in the cumulus–oocyte complex during folliculogenesis: A review

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