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Shared aspects of mRNA expression associated with oocyte maturation failure in humans and rhesus monkeys indicating compromised oocyte quality
Physiological Genomics ( IF 2.5 ) Pub Date : 2021-02-08 , DOI: 10.1152/physiolgenomics.00155.2020
Meghan L Ruebel 1 , Filippo Zambelli 2 , Peter Z Schall 1 , Montserrat Barragan 2 , Catherine A VandeVoort 3, 4 , Rita Vassena 2 , Keith E Latham 1
Affiliation  

Oocyte maturation failure observed in assisted reproduction technology (ART) cycles can limit the number of quality oocytes obtained and a pronounced barrier for some patients. The potential exists to use unmatured oocytes for ART through in vitro maturation. Understanding the molecular basis of oocyte maturation failure is pertinent to minimizing this loss of oocytes and considerations of whether such oocytes can be used safely for ART. We identified shared transcriptome abnormalities for rhesus monkey and human failed-to-mature (FTM) oocytes relative to healthy matured MII stage oocytes. We discovered that, although the number of shared affected genes was comparatively small, FTM oocytes in both species shared effects for several pathways and functions, including predicted activation of oxidative phosphorylation (OxPhos) with additional effects on mitochondrial function, lipid metabolism, transcription, nucleotide excision repair, endoplasmic reticulum stress, unfolded protein response, and cell viability. RICTOR emerged as a prominent upstream regulator with predicted inhibition across all analyses. Alterations in KDM5A, MTOR, MTORC1, INSR, CAB39L and STK11 activities were implicated along with RICTOR in modulating mitochondrial activity and OxPhos. Defects in cell cycle progression were not a prominent feature of FTM oocytes. These results identify a common set of transcriptome abnormalities associated with oocyte maturation failure. While our results do not demonstrate causality, they indicate that fundamental aspects of cellular function are abnormal in FTM oocytes, and raise significant concerns about the potential risks of using FTM oocytes for ART.

中文翻译:

人类和恒河猴中与卵母细胞成熟失败相关的 mRNA 表达的共同方面表明卵母细胞质量受损

在辅助生殖技术 (ART) 周期中观察到的卵母细胞成熟失败可能会限制获得的优质卵母细胞的数量,并且对某些患者来说是一个明显的障碍。存在通过体外成熟使用未成熟卵母细胞进行抗逆转录病毒疗法的潜力。了解卵母细胞成熟失败的分子基础有助于最大限度地减少这种卵母细胞的损失,并考虑这些卵母细胞是否可以安全地用于 ART。我们确定了恒河猴和人类未成熟(FTM)卵母细胞相对于健康成熟的 MII 阶段卵母细胞的共同转录组异常。我们发现,虽然共享的受影响基因的数量相对较少,但两个物种中的 FTM 卵母细胞对几种途径和功能都有共同的影响,包括预测的氧化磷酸化 (OxPhos) 激活,对线粒体功能、脂质代谢、转录、核苷酸切除修复、内质网应激、未折叠蛋白反应和细胞活力有额外影响。RICTOR 成为一个突出的上游调节剂,在所有分析中都具有预测抑制作用。KDM5A、MTOR、MTORC1、INSR、CAB39L 和 STK11 活性的改变与 RICTOR 一起参与调节线粒体活性和 OxPhos。细胞周期进程的缺陷不是 FTM 卵母细胞的突出特征。这些结果确定了一组与卵母细胞成熟失败相关的常见转录组异常。虽然我们的结果没有证明因果关系,但它们表明 FTM 卵母细胞中细胞功能的基本方面是异常的,
更新日期:2021-02-09
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