BACKGROUND Millions of children have been born throughout the world thanks to ARTs, the harmlessness of which has not yet been fully demonstrated. For years, efforts to evaluate the specific effects of ART have focused on the embryo; however, it is the oocyte quality that mainly dictates first and foremost the developmental potential of the future embryo. Ovarian stimulation, cryopreservation, and IVM are sometimes necessary steps to obtain a mature oocyte, but they could alter the appropriate expression of the oocyte genome. Additionally, it is likely that female infertility, environmental factors, and lifestyle have a significant influence on oocyte transcriptomic quality, which may interfere with the outcome of an ART attempt. OBJECTIVE AND RATIONALE The objective of this review is to identify transcriptomic changes in the human oocyte caused by interventions specific to ART but also intrinsic factors such as age, reproductive health issues, and lifestyle. We also provide recommendations for future good practices to be conducted when attempting ART. SEARCH METHODS An in-depth literature search was performed on PubMed to identify studies assessing the human oocyte transcriptome following ART interventions, or in the context of maternal aging, suboptimal lifestyle, or reproductive health issues. OUTCOMES ART success is susceptible to external factors, maternal aging, lifestyle factors (smoking, BMI), and infertility due to endometriosis or polycystic ovary syndrome. Indeed, all of these are likely to increase oxidative stress and alter mitochondrial processes in the foreground. Concerning ART techniques themselves, there is evidence that different ovarian stimulation regimens shape the oocyte transcriptome. The perturbation of processes related to the mitochondrion, oxidative phosphorylation, and metabolism is observed with IVM. Cryopreservation might dysregulate genes belonging to transcriptional regulation, ubiquitination, cell cycle, and oocyte growth pathways. For other ART laboratory factors such as temperature, oxygen tension, air pollution, and light, the evidence remains scarce. Focusing on genes involved in chromatin-based processes such as DNA methylation, heterochromatin modulation, histone modification, and chromatin remodeling complexes, but also genomic imprinting, we observed systematic dysregulation of such genes either after ART intervention or lifestyle exposure, as well as due to internal factors such as maternal aging and reproductive diseases. Alteration in the expression of such epigenetic regulators may be a common mechanism linked to adverse oocyte environments, explaining global transcriptomic modifications. WIDER IMPLICATIONS Many IVF factors and additional external factors have the potential to impair oocyte transcriptomic integrity, which might not be innocuous for the developing embryo. Fortunately, it is likely that such dysregulations can be minimized by adapting ART protocols or reducing adverse exposure.

中文翻译：

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ART 中使用的人卵母细胞的转录组完整性：技术和内在因素效应。


背景 由于 ART 治疗，全世界有数百万儿童出生，但其无害性尚未得到充分证明。多年来，评估 ART 具体效果的努力一直集中在胚胎上;然而，卵母细胞的质量首先决定了未来胚胎的发育潜力。卵巢刺激、冷冻保存和 IVM 有时是获得成熟卵母细胞的必要步骤，但它们可能会改变卵母细胞基因组的适当表达。此外，女性不孕症、环境因素和生活方式可能对卵母细胞转录组质量有重大影响，这可能会干扰 ART 尝试的结果。客观和基本原理 本综述的目的是确定由 ART 特异性干预措施以及内在因素（如年龄、生殖健康问题和生活方式）引起的人类卵母细胞转录组变化。我们还为未来尝试 ART 时应采取的良好实践提供了建议。检索方法 在 PubMed 上进行了深入的文献检索，以确定在 ART 干预后或在孕产妇衰老、次优生活方式或生殖健康问题的情况下评估人类卵母细胞转录组的研究。结果 ART 的成功容易受到外部因素、孕产妇衰老、生活方式因素（吸烟、BMI）以及子宫内膜异位症或多囊卵巢综合征引起的不孕症的影响。事实上，所有这些都可能会增加氧化应激并改变前景中的线粒体过程。关于 ART 技术本身，有证据表明不同的卵巢刺激方案塑造了卵母细胞转录组。 用 IVM 观察到与线粒体、氧化磷酸化和代谢相关的过程的扰动。冷冻保存可能会使属于转录调控、泛素化、细胞周期和卵母细胞生长途径的基因失调。对于其他 ART 实验室因素，例如温度、氧分度、空气污染和光线，证据仍然很少。专注于参与基于染色质的过程的基因，例如 DNA 甲基化、异染色质调节、组蛋白修饰和染色质重塑复合物，以及基因组印记，我们观察到这些基因在 ART 干预或生活方式暴露后以及由于内部因素（如孕产妇衰老和生殖疾病）而出现系统性失调。这种表观遗传调节因子表达的改变可能是与不利卵母细胞环境相关的常见机制，解释了整体转录组修饰。更广泛的影响 许多 IVF 因素和其他外部因素有可能损害卵母细胞转录组的完整性，这对发育中的胚胎可能并非无害。幸运的是，通过调整 ART 方案或减少不良暴露，可以最大限度地减少这种失调。