Essential shared and species-specific features of mammalian oocyte maturation-associated transcriptome changes impacting oocyte physiology

Author(s):  
Peter Z Schall ◽  
Keith E. Latham

Oogenesis is a complex process resulting in the production of a truly remarkable cell-the oocyte. Oocytes execute many unique processes and functions such as meiotic segregation of maternal genetic material, and essential life-generating functions after fertilization including post-transcriptional support of essential homeostatic and metabolic processes, and activation and reprogramming of the embryonic genome. An essential goal for understanding female fertility and infertility in mammals is to discover critical features driving the production of quality oocytes, particularly the complex regulation of oocyte maternal mRNAs. We report here the first in-depth meta-analysis of oocyte maturation-associated transcriptome changes, using eight data sets encompassing 94 RNAseq libraries for human, rhesus monkey, mouse, and cow. A majority of maternal mRNAs are regulated in a species-restricted manner, highlighting considerable divergence in oocyte transcriptome handling during maturation. We identified 121 mRNAs changing in relative abundance similarly across all four species (92 of high homology), and 993 (670 high homology) mRNAs regulated similarly in at least three of the four species, corresponding to just 0.84% and 6.9% of mRNAs analyzed. Ingenuity Pathway Analysis (IPA) revealed an association of these shared mRNAs with many shared pathways and functions, most prominently oxidative phosphorylation and mitochondrial function. These shared functions were reinforced further by primate-specific and species-specific DEGs. Thus, correct down-regulation of mRNAs related to oxidative phosphorylation and mitochondrial function is a major shared feature of mammalian oocyte maturation.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Bethany Muller ◽  
Niamh Lewis ◽  
Tope Adeniyi ◽  
Henry J. Leese ◽  
Daniel R. Brison ◽  
...  

AbstractMitochondria provide the major source of ATP for mammalian oocyte maturation and early embryo development. Oxygen Consumption Rate (OCR) is an established measure of mitochondrial function. OCR by mammalian oocytes and embryos has generally been restricted to overall uptake and detailed understanding of the components of OCR dedicated to specific molecular events remains lacking. Here, extracellular flux analysis (EFA) was applied to small groups of bovine, equine, mouse and human oocytes and bovine early embryos to measure OCR and its components. Using EFA, we report the changes in mitochondrial activity during the processes of oocyte maturation, fertilisation, and pre-implantation development to blastocyst stage in response to physiological demands in mammalian embryos. Crucially, we describe the real time partitioning of overall OCR to spare capacity, proton leak, non-mitochondrial and coupled respiration – showing that while activity changes over the course of development in response to physiological demand, the overall efficiency is unchanged. EFA is shown to be able to measure mitochondrial function in small groups of mammalian oocytes and embryos in a manner which is robust, rapid and easy to use. EFA is non-invasive and allows real-time determination of the impact of compounds on OCR, facilitating an assessment of the components of mitochondrial activity. This provides proof-of-concept for EFA as an accessible system with which to study mammalian oocyte and embryo metabolism.


2021 ◽  
pp. 1-10
Author(s):  
Wei Qin ◽  
Wenwen Li ◽  
Qi Wang ◽  
Min Gong ◽  
Tingting Li ◽  
...  

Background: The global race-dependent association of Alzheimer’s disease (AD) and apolipoprotein E (APOE) genotype is not well understood. Transethnic analysis of APOE could clarify the role of genetics in AD risk across populations. Objective: This study aims to determine how race and APOE genotype affect the risks for AD. Methods: We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library since 1993 to Aug 25, 2020. A total of 10,395 reports were identified, and 133 were eligible for analysis with data on 77,402 participants. Studies contained AD clinical diagnostic and APOE genotype data. Homogeneous data sets were pooled in case-control analyses. Odds ratios and 95% confidence intervals for developing AD were calculated for populations of different races and APOE genotypes. Results: The proportion of APOE genotypes and alleles differed between populations of different races. Results showed that APOE ɛ4 was a risk factor for AD, whereas APOE ɛ2 protected against it. The effects of APOE ɛ4 and ɛ2 on AD risk were distinct in various races, they were substantially attenuated among Black people. Sub-group analysis found a higher frequency of APOE ɛ4/ɛ4 and lower frequency of APOE ɛ3/ɛ3 among early-onset AD than late-onset AD in a combined group and different races. Conclusion: Our meta-analysis suggests that the association of APOE genotypes and AD differ between races. These results enhance our understanding of APOE-related risk for AD across race backgrounds and provide new insights into precision medicine for AD.


Author(s):  
Sicong Yu ◽  
Lepeng Gao ◽  
Yang Song ◽  
Xin Ma ◽  
Shuang Liang ◽  
...  

Abstract Mitochondria play an important role in controlling oocyte developmental competence. Our previous studies showed that glycine can regulate mitochondrial function and improve oocyte maturation in vitro. However, the mechanisms by which glycine affects mitochondrial function during oocyte maturation in vitro have not been fully investigated. In this study, we induced a mitochondrial damage model in oocytes with the Bcl-2-specific antagonist ABT-199. We investigated whether glycine could reverse the mitochondrial dysfunction induced by ABT-199 exposure and whether it is related to calcium regulation. Our results showed that ABT-199 inhibited cumulus expansion, decreased the oocyte maturation rate and the intracellular glutathione (GSH) level, caused mitochondrial dysfunction, induced oxidative stress, which was confirmed by decreased mitochondrial membrane potential (Δ⍦m) and the expression of mitochondrial function-related genes (PGC-1α), and increased reactive oxygen species (ROS) levels and the expression of apoptosis-associated genes (Bax, caspase-3, CytC). More importantly, ABT-199-treated oocytes showed an increase in the intracellular free calcium concentration ([Ca 2+]i) and had impaired cortical type 1 inositol 1,4,5-trisphosphate receptors (IP3R1) distribution. Nevertheless, treatment with glycine significantly ameliorated mitochondrial dysfunction, oxidative stress and apoptosis, glycine also regulated [Ca 2+]i levels and IP3R1 cellular distribution, which further protects oocyte maturation in ABT-199-induced porcine oocytes. Taken together, our results indicate that glycine has a protective action against ABT-199-induced mitochondrial dysfunction in porcine oocytes.


2021 ◽  
pp. 027112142110327
Author(s):  
Esther R. Lindström ◽  
Jason C. Chow ◽  
Kathleen N. Zimmerman ◽  
Hongyang Zhao ◽  
Elise Settanni ◽  
...  

Engagement in early childhood has been linked with later achievement, but the relation between these variables and how they are measured in early childhood requires examination. We estimated the overall association between academic engagement and achievement in children prior to kindergarten entry. Our systematic literature search yielded 13,521 reports for structured eligibility screening; from this pool of studies, we identified 21 unique data sets, with 199 effect sizes for analysis. We coded eligible studies, extracted effect sizes, accounted for effect size dependency, and used random-effects models to synthesize findings. The overall correlation between academic engagement and achievement was r = .24 (range: −.08 to −.71), and moderator analyses did not significantly predict the relation between the two constructs. This study aligns with previous research on this topic and examines issues related to these measures, their constraints, and applications as they pertain to early childhood research.


2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Konstantinos Voutetakis ◽  
Aristotelis Chatziioannou ◽  
Efstathios S. Gonos ◽  
Ioannis P. Trougakos

Several studies have employed DNA microarrays to identify gene expression signatures that mark human ageing; yet the features underlying this complicated phenomenon remain elusive. We thus conducted a bioinformatics meta-analysis on transcriptomics data from human cell- and biopsy-based microarrays experiments studying cellular senescence orin vivotissue ageing, respectively. We report that coregulated genes in the postmitotic muscle and nervous tissues are classified into pathways involved in cancer, focal adhesion, actin cytoskeleton, MAPK signalling, and metabolism regulation. Genes that are differentially regulated during cellular senescence refer to pathways involved in neurodegeneration, focal adhesion, actin cytoskeleton, proteasome, cell cycle, DNA replication, and oxidative phosphorylation. Finally, we revealed genes and pathways (referring to cancer, Huntington’s disease, MAPK signalling, focal adhesion, actin cytoskeleton, oxidative phosphorylation, and metabolic signalling) that are coregulated during cellular senescence andin vivotissue ageing. The molecular commonalities between cellular senescence and tissue ageing are also highlighted by the fact that pathways that were overrepresented exclusively in the biopsy- or cell-based datasets are modules either of the same reference pathway (e.g., metabolism) or of closely interrelated pathways (e.g., thyroid cancer and melanoma). Our reported meta-analysis has revealed novel age-related genes, setting thus the basis for more detailed future functional studies.


2012 ◽  
Vol 132 (2) ◽  
pp. 485-487 ◽  
Author(s):  
Matthew H. Law ◽  
Grant W. Montgomery ◽  
Kevin M. Brown ◽  
Nicholas G. Martin ◽  
Graham J. Mann ◽  
...  

2002 ◽  
Vol 2 ◽  
pp. 169-189 ◽  
Author(s):  
Lawrence W. Barnthouse ◽  
Douglas G. Heimbuch ◽  
Vaughn C. Anthony ◽  
Ray W. Hilborn ◽  
Ransom A. Myers

We evaluated the impacts of entrainment and impingement at the Salem Generating Station on fish populations and communities in the Delaware Estuary. In the absence of an agreed-upon regulatory definition of “adverse environmental impact” (AEI), we developed three independent benchmarks of AEI based on observed or predicted changes that could threaten the sustainability of a population or the integrity of a community.Our benchmarks of AEI included: (1) disruption of the balanced indigenous community of fish in the vicinity of Salem (the “BIC” analysis); (2) a continued downward trend in the abundance of one or more susceptible fish species (the “Trends” analysis); and (3) occurrence of entrainment/impingement mortality sufficient, in combination with fishing mortality, to jeopardize the future sustainability of one or more populations (the “Stock Jeopardy” analysis).The BIC analysis utilized nearly 30 years of species presence/absence data collected in the immediate vicinity of Salem. The Trends analysis examined three independent data sets that document trends in the abundance of juvenile fish throughout the estuary over the past 20 years. The Stock Jeopardy analysis used two different assessment models to quantify potential long-term impacts of entrainment and impingement on susceptible fish populations. For one of these models, the compensatory capacities of the modeled species were quantified through meta-analysis of spawner-recruit data available for several hundred fish stocks.All three analyses indicated that the fish populations and communities of the Delaware Estuary are healthy and show no evidence of an adverse impact due to Salem. Although the specific models and analyses used at Salem are not applicable to every facility, we believe that a weight of evidence approach that evaluates multiple benchmarks of AEI using both retrospective and predictive methods is the best approach for assessing entrainment and impingement impacts at existing facilities.


2015 ◽  
Vol 135 (10) ◽  
pp. 2455-2463 ◽  
Author(s):  
Lanlan Yin ◽  
Sergio G. Coelho ◽  
Julio C. Valencia ◽  
Dominik Ebsen ◽  
Andre Mahns ◽  
...  

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