Evaluate the developmental competence of human 8-cell embryos by single-cell RNA sequencing.

Weizhou Wang, Mengmeng Zhao, Haiyang Zuo, Jingyao Zhang, Bin Liu, Fu Chen, Pengyun Ji, Guoshi Liu, Shuai Gao, Wei Shang, Lu Zhang
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引用次数: 0

Abstract

Abstract: The transition of maternal to zygotic gene expression regulation is critical for human preimplantation embryo development. In recent years, single-cell RNA sequencing (scRNA-seq) had been applied to detect the factors that regulate human oocyte maturation and early embryo development. Here, the evaluation of transcriptomes in single blastomere from the embryo collected from patients by scRNA-seq was performed. There were 20 blastomeres biopsied from 8-cell embryos of seven patients who received more than two ART cycles due to low embryo competence. Meanwhile, ten cells were collected from 8-cell embryos of four patients who received ART treatment due to male or tubal factors. The blastomeres were then evaluated using the previously established scRNA-seq method to determine the associations between their gene expression and developmental competence. The total number of genes detected in 8-cell embryos that failed to form blastocyst including maternal and zygotic mRNAs was reduced. There were 324 differently expressed genes detected among the 8-cell embryos including 65 genes that were significantly suppressed in the 8-cell embryos that failed to form blastocyst. Further analysis found these 8-cell embryos arrested at the cleavage stage due to the dysfunction of the cell cycle, DNA transcription activity, histone methylation, and cell division-related genes such as SMCO-1, ZNF271P,ZNF679, ASF1b, BEX3, DPPA2, and ORC4. The alterations of gene expression detected in human 8-cell embryos are tightly associated with its developmental competence and could be used as targets to enhance embryo development or parameters to predict the embryo's development outcomes.

Lay summary: Many females are suffering infertility due to the failure of embryonic development at early stages due to unknown causes. At the very beginning of human embryo development, the embryos start to express its own genes, which should be achieved at 8-cell stage. In current research, we isolated one cell from 8-cell embryos and detected the gene expression at single-cell level. Then the remaining cells of these embryos were cultured to form blastocyst. Meanwhile, the data was analyzed according to the outcomes of embryo development. We detected 324 differently expressed genes between the 8-cell embryos that succeeded and failed to form blastocyst. Our research showed the association between the gene expression and the developmental competence of 8-cell embryos. The findings could be used to predict the embryo quality and potential therapy target to improve the efficiency of assisted reproductive techniques.

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单细胞RNA测序评价人8细胞胚胎发育能力。
摘要:母体向合子基因表达调控的转变对人类着床前胚胎发育至关重要。近年来,单细胞RNA测序(scRNA-seq)被用于检测人类卵母细胞成熟和早期胚胎发育的调控因素。本研究利用scRNA-seq技术对患者胚胎中单个卵裂球的转录组进行了评估。由于胚胎能力低下,7例患者接受了2个以上的抗逆转录病毒治疗周期,其中8个细胞的胚胎有20个卵裂球活检。同时,从4名因男性或输卵管因素接受ART治疗的患者的8个细胞胚胎中收集10个细胞。然后使用先前建立的scRNA-seq方法对卵裂球进行评估,以确定其基因表达与发育能力之间的关系。在8个细胞胚胎中检测到的不能形成囊胚的基因总数减少,包括母系和合子mrna。在8细胞胚胎中检测到324个不同表达的基因,其中65个基因在未形成囊胚的8细胞胚胎中被显著抑制。进一步分析发现,由于细胞周期、DNA转录活性、组蛋白甲基化和细胞分裂相关基因(如SMCO-1、ZNF271P、ZNF679、ASF1b、BEX3、DPPA2和ORC4)的功能障碍,这些8个细胞胚胎在卵裂阶段停滞。在人类8细胞胚胎中检测到的基因表达改变与其发育能力密切相关,可以作为促进胚胎发育的靶点或预测胚胎发育结果的参数。概要:许多女性由于未知原因导致早期胚胎发育失败而遭受不孕。在人类胚胎发育的最初阶段,胚胎开始表达自己的基因,这应该在8细胞阶段实现。在目前的研究中,我们从8个细胞胚胎中分离一个细胞,并在单细胞水平上检测基因表达。然后将这些胚胎的剩余细胞培养成囊胚。同时,根据胚胎发育结果对数据进行分析。我们在成功形成囊胚和失败形成囊胚的8个细胞胚胎中检测到324个不同表达的基因。我们的研究显示了基因表达与8细胞胚胎发育能力之间的关系。研究结果可用于预测胚胎质量和潜在的治疗靶点,以提高辅助生殖技术的效率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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