Mechanical stress accompanied with nuclear rotation is involved in the dormant state of mouse oocytes

Nagamatsu, Go; Shimamoto, So; Hamazaki, Nobuhiko; Nishimura, Yukio; Hayashi, Kozaburo

doi:10.1126/sciadv.aav9960

Cited by 101 publications

(92 citation statements)

References 40 publications

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“…Knowledge from our and subsequent studies may aid in the production of quiescent primordial follicles in vitro, which will be useful not only for scientific research but also for medical and industrial applications. In this regard, recent papers from Hayashi's laboratory reported that hypoxia and mechanical stress play important roles in the formation and the maintenance of primordial follicles during this revision [62,63]. Taken together with these novel findings, further studies should be addressed to reveal the mechanisms of this developmental process.…”

Section: Discussionmentioning

confidence: 87%

ELAVL2‐directed RNA regulatory network drives the formation of quiescent primordial follicles

et al. 2019

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Formation of primordial follicles is a fundamental, early process in mammalian oogenesis. However, little is known about the underlying mechanisms. We herein report that the RNA‐binding proteins ELAVL2 and DDX6 are indispensable for the formation of quiescent primordial follicles in mouse ovaries. We show that Elavl2 knockout females are infertile due to defective primordial follicle formation. ELAVL2 associates with mRNAs encoding components of P‐bodies (cytoplasmic RNP granules involved in the decay and storage of RNA) and directs the assembly of P‐body‐like granules by promoting the translation of DDX6 in oocytes prior to the formation of primordial follicles. Deletion of Ddx6 disturbs the assembly of P‐body‐like granules and severely impairs the formation of primordial follicles, indicating the potential importance of P‐body‐like granules in the formation of primordial follicles. Furthermore, Ddx6‐deficient oocytes are abnormally enlarged due to misregulated PI3K‐AKT signaling. Our data reveal that an ELAVL2‐directed post‐transcriptional network is essential for the formation of quiescent primordial follicles.

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Section: Discussionmentioning

confidence: 87%

ELAVL2‐directed RNA regulatory network drives the formation of quiescent primordial follicles

et al. 2019

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“…The decrease in pYAP-induced proliferation and growth of granulosa cells and follicle activation in fragmented grafts. The importance of the physical environment provided by the extracellular matrix is also highlighted by another recent study which demonstrated that mechanical stress plays a key role in maintaining follicle dormancy and that reduction of this stress triggers follicle activation and growth (Nagamatsu et al 2019).…”

Section: Causes Of Transplantation-induced Primordial Follicle Lossmentioning

confidence: 97%

FERTILITY PRESERVATION: Follicle reserve loss in ovarian tissue transplantation

Roness

Meirow

2019

Reproduction

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Ovarian tissue cryopreservation and transplantation (OTCP-TP) has progressed over the past decade from a revolutionary experimental procedure to a well-accepted treatment in many centers for young patients with a high risk of ovarian failure after cancer treatment. The procedure is remarkably successful, with studies reporting return of ovarian function in up to 95% of graft recipients and pregnancy rates of between 30 and 50%. The most significant limitation of OTCP-TP is the massive loss of follicles that occurs following transplantation, which is primarily attributed to ischemic damage and follicle activation. We review the current approaches to reducing follicle loss and maximizing graft lifespan via pharmacological agents which reduce ischemic damage and follicle activation. We further discuss the value and disadvantage of inducing follicle activation in the graft as a means of generating mature follicles in the immediate short term.

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“…Disruption of the FOXO3a gene in mice accelerates primordial follicle growth and addition of FOXO3a inhibits it (Castrillon et al 2003;Liu et al 2007). Digestion of the ovary with collagenase IV and trypsin released the primordial follicles of the ECM-associated stress as indicated by loosening of actin stress fibers and a progression in granulosa cell morphology from squamous to cuboidal (Nagamatsu et al 2019). Additionally, FOXO3a was exported from the nucleus to the cytoplasm, an additional indication of follicle activation in primordial to growing follicles in mice.…”

Section: Compartmentalization and Physical Featuresmentioning

confidence: 99%

Tissue Engineered Ovary

Laronda

2020

Organ Tissue Engineering

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An engineered ovary could benefit a variety of patients with ovarian insufficiency including those with an inherited condition, de novo mutation, or those whose treatment regimens could reduce ovarian function. This chapter highlights the impact of developing an engineered ovary, highlights the important features of an ovary to be recreated, and reviews the current state of fertility preservation. Encapsulating hydrogels and scaffolds have been used to restore ovarian hormones and fertility in animal models and to monitor in vitro growth of human ovarian cells. Additional advancements to these technologies will rely on an understanding of ovarian biology in order to recapitulate and restore long-term and physiological function. Considerations for the different microenvironments within the cortical and medullar compartments and cell types that support oocyte maturation, including granulosa and heterogeneous stromal cells, will be essential for recreating appropriate folliculogenesis. Mechanical cues and facilitation of paracrine and endocrine signals to reach target cells can also be tailored within engineered environments. These studies may one day improve the current fertility restoration options or even provide options for patients that currently lack options.

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Mechanical stress accompanied with nuclear rotation is involved in the dormant state of mouse oocytes

Cited by 101 publications

References 40 publications

ELAVL2‐directed RNA regulatory network drives the formation of quiescent primordial follicles

ELAVL2‐directed RNA regulatory network drives the formation of quiescent primordial follicles

FERTILITY PRESERVATION: Follicle reserve loss in ovarian tissue transplantation

Tissue Engineered Ovary

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