Identification and characterization of Aurora kinase B and C variants associated with maternal aneuploidy

Nguyen, Alexandra L.; Marín, Diego; Zhou, Anbo; Gentilello, Amanda S.; Smoak, Evan M.; Cao, Zubing; Fedick, Anastasia; Wang, Yujue; Taylor, Deanne; Scott, Richard T.; Xing, Jinchuan; Treff, Nathan R.; Schindler, Karen

doi:10.1093/molehr/gax018

Cited by 30 publications

(14 citation statements)

References 62 publications

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“…Although increased risk of aneuploidy is strongly correlated with increasing maternal age, significant variation exists in aneuploid conception rates of IVF patients without any reproductive pathology at any given age. [73][74][75][76][77] Indeed, some of the first genetic surveys of human preimplantation embryos noted that certain patients appeared to be predisposed to generating embryos with complex forms of mosaic aneuploidy (i.e., "chaotic mosaicism"), independent of maternal age. 78 Similar observations have been noted with respect to oocyte and sperm aneuploidies of meiotic origin, including in recent studies.…”

Section: Genetic Contributions and Pathways Associated With Aneuplomentioning

confidence: 99%

Origins and mechanisms leading to aneuploidy in human eggs

et al. 2021

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The gain or loss of a chromosome-or aneuploidy-acts as one of the major triggers for infertility and pregnancy loss in humans. These chromosomal abnormalities affect more than 40% of eggs in women at both ends of the age spectrum, that is, young girls as well as women of advancing maternal age. Recent studies in human oocytes and embryos using genomics, cytogenetics, and in silico modeling all provide new insight into the rates and potential genetic and cellular factors associated with aneuploidy at varying stages of development. Here, we review recent studies that are shedding light on potential molecular mechanisms of chromosome missegregation in oocytes and embryos across the entire female reproductive life span.

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Section: Genetic Contributions and Pathways Associated With Aneuplomentioning

confidence: 99%

Origins and mechanisms leading to aneuploidy in human eggs

et al. 2021

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“…It is a key regulator of oocyte meiosis, and essential for the correct chromosome alignment and segregation (Nguyen et al, 2018). Loss of Aurkc results in misaligned chromosomes, failed cytokinesis and arrest of oocyte development with significantly less embryos developed to the blastocysts (Nguyen et al, 2017; Schindler et al, 2012). Upregulation of Aurkc causes germ cell arrest at the first metaphase stage because of defects in chromosome segregation and failed cytokinesis (Willems et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Reduced growth capacity of preimplantation mouse embryos in chronic unpredictable stress model

Zhao

Zhang

et al. 2020

Molecular Reproduction Devel

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Psychological stress can affect female reproduction by deteriorating oocyte quality, but the molecular mechanism is unclear. In this study, we used the chronic unpredictable stress model to study the effect of psychological stress on mouse oocyte competence during preimplantation stage, and RNA sequencing in single oocytes to analyze differential gene expression at the transcription level. Stress changed the serum levels of glucocorticoids and reduced oocyte developmental potential, depending on the strength of the stress. Strong stress (two stressors per day) reduced the fertilization rate and induced significant apoptosis in blastocysts. Moderate stress (one stressor per day) reduced the cleavage rate and blastocyst formation rate. Weak stress (one stressor every 2 days) did not have any significant negative effect on the fertilization, cleavage, and blastocyst formation. Hatching rate was not affected by stress, but stress retarded the development of the expanded blastocysts and inhibited the embryo development at early stages. Transcriptome analysis revealed that stress disturbed the expression of cell cycle regulators and apoptotic genes. The hub genes identified through protein‐protein interaction analysis include Msln, Ceacam12, Psg16, Psg17, and Psg23, which are all carcinoembryonic or related genes involved in cell adhesion, proliferation, and migration. Thus, stress was inhibitory on fertilization and early embryo development in mice.

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“…Of note, CRISPR/Cas9 was recently used to AID-tag endogenous Sox2 , Gata6 , and Nanog , and to express a TIR1 transgene under the actin β promoter in mouse embryos [29]. A different application of this auxin-inducible degradation method is the removal of exogenously expressed proteins, as described here, which can be used for manipulation of molecules and pathways of interest using phosphomimic, dominant-negative, or constitutively active variants [9, 35–40]. The addition of an AID tag to exogenously expressed proteins allows for further manipulation in oocytes during progression through meiosis.…”

Section: Discussionmentioning

confidence: 99%

Auxin-inducible protein degradation as a novel approach for protein depletion and reverse genetic discoveries in mammalian oocytes†

Camlin

Evans

2019

Biology of Reproduction

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The disruption of protein expression is a major approach used for investigating protein function in mammalian oocytes. This is often achieved with RNAi/morpholino-mediated knockdown or gene knockout, leading to long-term loss of proteins of interest. However, these methods have noteworthy limitations, including (a) slow protein turnover can prohibit use of these approaches; (b) essential roles in early events precludes characterization of functions in subsequent events; (c) extended protein loss can allow time for compensatory mechanisms and other unanticipated events that confound interpretation of results. The work presented here examines the use of auxin-inducible degradation, a powerful new approach that overcomes these limitations through the depletion of one's protein of interest through controllable ubiquitin-mediated degradation. This method has been employed in yeast and mammalian cell lines, and here we demonstrate the utility of auxin-inducible degradation in mouse oocytes at multiple stages of meiosis, through degradation of exogenously expressed EGFP. We also evaluate important parameters for experimental design for use of this system in oocytes. This study thus expands the toolkit of researchers in oocyte biology, establishing the use of this unique and versatile approach for depleting proteins in oocytes, and providing researchers with valuable information to make use of this system.

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Identification and characterization of Aurora kinase B and C variants associated with maternal aneuploidy

Cited by 30 publications

References 62 publications

Origins and mechanisms leading to aneuploidy in human eggs

Origins and mechanisms leading to aneuploidy in human eggs

Reduced growth capacity of preimplantation mouse embryos in chronic unpredictable stress model

Auxin-inducible protein degradation as a novel approach for protein depletion and reverse genetic discoveries in mammalian oocytes†

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