Age-related integrative transcriptomic profiling of human granulosa cells reveals mRNA-microRNA regulatory network associated with key ovulation dynamics†.

IF 3.1 2区 生物学 Q2 REPRODUCTIVE BIOLOGY
Heather M Rogers, Ahmed Gad, Gentry K Cork, Nico G Menjivar, William B Schoolcraft, Dawit Tesfaye, Ye Yuan
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Abstract

Advanced maternal age (AMA) patients experience decreased success from assisted reproductive technologies (ART), attributed to the quantity and quality of oocytes, which is significantly influenced by the intrafollicular granulosa cells (GCs). In this study, we compared the mRNA and microRNA (miRNA) transcriptomes between young (< 32 years old) and AMA (> 38 years old) patients' GCs to identify potential ovarian aging-related molecular signatures. We identified 293 and 21 differentially expressed genes (DEGs) and miRNAs (DE miRNAs), respectively, between young and aged GCs. Highly expressed mitochondrial-encoded genes, MT-ND3, MT-ND6, and MT-CYB, were downregulated in aged GCs, indicating potential mitochondrial insufficiency. Additionally, pathway analysis indicates DEGs are involved in inflammation, cytokine signaling, extracellular matrix (ECM) remodeling, and angiogenesis. Key DEGs related to these processes include CXCL8, IL1B, NLRP3, SIGIRR, ANGPT2, ADAM8, and ADAMTS14. Additionally, target gene prediction and pathway analysis of DE miRNAs indicates their potential post-transcriptional regulation of genes associated with cell signaling, mitochondrial function, oxidative stress, apoptosis, and senescence pathways in addition to cytokine signaling, angiogenesis, and ECM remodeling. To investigate regulatory mechanisms further, we looked at the DEGs' convergence with the DE miRNAs predicted target genes and we identified miR-483-3p, miR-1268a, miR-4497, miR-7704, miR-135a-5p, miR-1261, and miR-4791 as potential crucial regulators of genes involved in pathways associated with inflammation, ECM, and angiogenesis. This data suggests that aged GCs have an impaired ability to elicit the same pro-inflammatory response combined with dysregulation of angiogenesis and ECM remodeling compared to young GCs, and miRNA may play a role in regulating key ovulatory processes. While this study identifies potential regulatory relationships between DE miRNAs and DEGs, experimental validation is necessary to confirm the relationships and biological relevance.

与年龄相关的人类颗粒细胞综合转录组分析揭示了与关键排卵动态相关的 mRNA-microRNA调控网络
高龄产妇(AMA)患者使用辅助生殖技术(ART)的成功率较低,原因是卵母细胞的数量和质量受到卵泡内颗粒细胞(GCs)的显著影响。在本研究中,我们比较了年轻(< 32岁)和老年(> 38岁)患者GCs的mRNA和microRNA (miRNA)转录组,以确定潜在的卵巢衰老相关分子特征。我们在年轻和老年GCs中分别鉴定了293个和21个差异表达基因(DEGs)和miRNAs (DE miRNAs)。高表达的线粒体编码基因MT-ND3、MT-ND6和MT-CYB在衰老的GCs中下调,表明可能存在线粒体功能不全。此外,通路分析表明,deg参与炎症、细胞因子信号传导、细胞外基质(ECM)重塑和血管生成。与这些过程相关的关键基因包括CXCL8、IL1B、NLRP3、SIGIRR、ANGPT2、ADAM8和ADAMTS14。此外,DE mirna的靶基因预测和通路分析表明,除了细胞因子信号传导、血管生成和ECM重塑外,它们还可能对细胞信号传导、线粒体功能、氧化应激、凋亡和衰老途径相关的基因进行转录后调控。为了进一步研究调控机制,我们研究了deg与DE mirna预测的靶基因的趋同,并确定了miR-483-3p、miR-1268a、miR-4497、miR-7704、miR-135a-5p、miR-1261和miR-4791是参与炎症、ECM和血管生成相关途径的基因的潜在关键调控因子。这些数据表明,与年轻的GCs相比,衰老的GCs引发相同的促炎反应、血管生成和ECM重塑失调的能力受损,miRNA可能在调节关键的排卵过程中发挥作用。虽然本研究确定了DE mirna和deg之间潜在的调节关系,但需要实验验证来确认这种关系和生物学相关性。
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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来源期刊
Biology of Reproduction
Biology of Reproduction 生物-生殖生物学
CiteScore
6.30
自引率
5.60%
发文量
214
审稿时长
1 months
期刊介绍: Biology of Reproduction (BOR) is the official journal of the Society for the Study of Reproduction and publishes original research on a broad range of topics in the field of reproductive biology, as well as reviews on topics of current importance or controversy. BOR is consistently one of the most highly cited journals publishing original research in the field of reproductive biology.
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