Analysis of single-cell RNA sequencing in human oocytes with diminished ovarian reserve uncovers mitochondrial dysregulation and translation deficiency.

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Reproductive Biology and Endocrinology Pub Date : 2024-11-15 DOI:10.1186/s12958-024-01321-8
Xin Li, Xingwu Wu, Hui Zhang, Peipei Liu, Leizhen Xia, Nana Zhang, Lifeng Tian, Zengming Li, Jing Lu, Yan Zhao, Jun Tan
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Abstract

Background: Diminished ovarian reserve (DOR) is clinically characterized by a decrease in the number of available ovarian follicles and a decline in the quality of oocytes, accompanied by hormonal changes. Low quality of DOR oocyte leads to impaired embryo development, an increased risk of aneuploid pregnancies and miscarriages. However, the specific pathogenic mechanism remains unclear, posing a significant challenge for assisted reproductive technology.

Methods: For the first time, our study employed single-cell RNA sequencing to reveal the altered transcriptomic landscape of DOR oocytes at GV stage after ovarian stimulation. Differentially expressed genes analysis (DEGs), functional enrichment analysis, weighted gene co-expression network analysis (WGCNA) and protein-protein interactions network analysis were performed.

Results: We found 132 up-regulated genes and 466 down-regulated genes in DOR oocytes, with the down-regulated genes primarily enriched in mitochondrial function and translation. Hub genes, identified through integrated analysis of WGCNA and DEGs, were further validated in DOR and control oocytes using RT-qPCR. By utilizing hub genes and employing transcription factor enrichment tools, it had been predicted that pleomorphic adenoma gene 1 (PLAG1) played a crucial role as a transcriptional regulatory factor in DOR oocytes. Additionally, we conformed the PLAG1-IGF2 axis was dysregulated in DOR oocytes.

Conclusions: Transcriptome analysis revealed that DOR oocytes exhibited mitochondrial dysfunction and translational defects, and the PLAG1-IGF2 axis might be a potential contributor for the low quality of DOR oocytes.

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对卵巢储备功能减退的人类卵母细胞进行单细胞 RNA 测序分析,发现线粒体失调和翻译缺陷。
背景:卵巢储备功能减退(DOR)的临床特征是可用卵泡数量减少,卵母细胞质量下降,并伴有激素变化。DOR卵母细胞质量低下会导致胚胎发育受损,增加非整倍体妊娠和流产的风险。然而,具体的致病机制仍不清楚,这给辅助生殖技术带来了巨大挑战:我们的研究首次采用单细胞 RNA 测序技术揭示了 DOR 卵母细胞在卵巢刺激后 GV 阶段的转录组变化。我们进行了差异表达基因分析(DEGs)、功能富集分析、加权基因共表达网络分析(WGCNA)和蛋白-蛋白相互作用网络分析:结果:我们发现DOR卵母细胞中有132个上调基因和466个下调基因,下调基因主要集中在线粒体功能和翻译方面。通过对 WGCNA 和 DEGs 的综合分析确定的枢纽基因,利用 RT-qPCR 在 DOR 和对照卵母细胞中得到了进一步验证。通过利用枢纽基因和转录因子富集工具,我们预测多形性腺瘤基因1(PLAG1)在DOR卵母细胞中作为转录调控因子发挥了关键作用。此外,我们还发现 PLAG1-IGF2 轴在 DOR 卵母细胞中调节失调:结论:转录组分析表明,DOR卵母细胞表现出线粒体功能障碍和翻译缺陷,PLAG1-IGF2轴可能是导致DOR卵母细胞质量低下的潜在因素。
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来源期刊
Reproductive Biology and Endocrinology
Reproductive Biology and Endocrinology 医学-内分泌学与代谢
CiteScore
7.90
自引率
2.30%
发文量
161
审稿时长
4-8 weeks
期刊介绍: Reproductive Biology and Endocrinology publishes and disseminates high-quality results from excellent research in the reproductive sciences. The journal publishes on topics covering gametogenesis, fertilization, early embryonic development, embryo-uterus interaction, reproductive development, pregnancy, uterine biology, endocrinology of reproduction, control of reproduction, reproductive immunology, neuroendocrinology, and veterinary and human reproductive medicine, including all vertebrate species.
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