Extracellular vesicles from cyclic mice modulate liver transcriptome in estroupause mice independent of age

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology Pub Date : 2025-02-25 DOI:10.1016/j.mce.2025.112508

Bianka M. Zanini , Bianca M. Ávila , Jéssica D. Hense , Driele N. Garcia , Sarah Ashiqueali , Pâmela I.C. Alves , Thais L. Oliveira , Tiago V. Collares , Miguel A. Brieño-Enríquez , Jeffrey B. Mason , Michal M. Masternak , Augusto Schneider

{"title":"Extracellular vesicles from cyclic mice modulate liver transcriptome in estroupause mice independent of age","authors":"Bianka M. Zanini , Bianca M. Ávila , Jéssica D. Hense , Driele N. Garcia , Sarah Ashiqueali , Pâmela I.C. Alves , Thais L. Oliveira , Tiago V. Collares , Miguel A. Brieño-Enríquez , Jeffrey B. Mason , Michal M. Masternak , Augusto Schneider","doi":"10.1016/j.mce.2025.112508","DOIUrl":null,"url":null,"abstract":"<div><div>Extracellular vesicles (EVs) of different sizes are secreted by cells and may contain microRNAs (miRNAs) among its cargo. These miRNAs in EVs can induce changes in gene expression and function of recipient cells. In different cells EVs content can change with age and physiological state affecting tissue function. Based on this, the aim of this study was to characterize the miRNA content and role of small EVs (sEVs) from cyclic female mice in the modulation of liver transcriptome in estropausal mice. Two-month-old female mice were induced to estropause using 4-vinylcyclohexene diepoxide (VCD). At six months of age, VCD-treated mice were divided into placebo group (VCD) and sEVs treated group (VCD + sEVs), which received 10 injections at 3-day intervals of sEVs isolated from serum of donor cyclic female mice. A group of cyclic mice also received placebo injection and served as controls (CTL). sEVs injection in mice undergoing estropause had no effect on body mass, insulin sensitivity or organ weight. We observed ten miRNAs differentially regulated in serum sEVs of VCD compared to CTL mice. In the liver we observed 931 genes differentially expressed in VCD + sEVs compared to VCD mice. Interestingly, eight pathways were up-regulated in liver by VCD treatment and down-regulated by sEVs treatment, indicating that sEVs from cyclic mice can reverse changes promoted by estropause in liver. The expression of <em>Cyp4a12a</em>, which is male-specific, was elevated in VCD females but not normalized by sEVs treatment. Our findings indicate that miRNA content in sEVs is regulated by estropause in mice independent of age. Additionally, treatment of estropausal mice with sEVs from cyclic mice can partially reverse changes in the liver transcriptome.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112508"},"PeriodicalIF":3.8000,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0303720725000590","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Extracellular vesicles (EVs) of different sizes are secreted by cells and may contain microRNAs (miRNAs) among its cargo. These miRNAs in EVs can induce changes in gene expression and function of recipient cells. In different cells EVs content can change with age and physiological state affecting tissue function. Based on this, the aim of this study was to characterize the miRNA content and role of small EVs (sEVs) from cyclic female mice in the modulation of liver transcriptome in estropausal mice. Two-month-old female mice were induced to estropause using 4-vinylcyclohexene diepoxide (VCD). At six months of age, VCD-treated mice were divided into placebo group (VCD) and sEVs treated group (VCD + sEVs), which received 10 injections at 3-day intervals of sEVs isolated from serum of donor cyclic female mice. A group of cyclic mice also received placebo injection and served as controls (CTL). sEVs injection in mice undergoing estropause had no effect on body mass, insulin sensitivity or organ weight. We observed ten miRNAs differentially regulated in serum sEVs of VCD compared to CTL mice. In the liver we observed 931 genes differentially expressed in VCD + sEVs compared to VCD mice. Interestingly, eight pathways were up-regulated in liver by VCD treatment and down-regulated by sEVs treatment, indicating that sEVs from cyclic mice can reverse changes promoted by estropause in liver. The expression of Cyp4a12a, which is male-specific, was elevated in VCD females but not normalized by sEVs treatment. Our findings indicate that miRNA content in sEVs is regulated by estropause in mice independent of age. Additionally, treatment of estropausal mice with sEVs from cyclic mice can partially reverse changes in the liver transcriptome.

查看原文本刊更多论文

周期小鼠的细胞外囊泡调节发情暂停小鼠的肝脏转录组，与年龄无关

细胞外囊泡（EVs）是由细胞分泌的不同大小的囊泡，其货物中可能含有microrna （mirna）。这些mirna可以诱导受体细胞的基因表达和功能发生变化。不同细胞中EVs含量随年龄和生理状态的变化而变化，影响组织功能。在此基础上，本研究的目的是表征周期雌性小鼠小ev （sev）在雌激素停运小鼠肝脏转录组调节中的miRNA含量及其作用。采用4-乙烯基二氧化环己烯（VCD）诱导2月龄雌性小鼠绝经。6月龄时，将VCD治疗小鼠分为安慰剂组（VCD）和sev治疗组（VCD + sev），每隔3天注射10次从供体雌性小鼠血清中分离的sev。一组循环小鼠也接受安慰剂注射并作为对照（CTL）。在绝经期小鼠中注射sEVs对体重、胰岛素敏感性和器官重量没有影响。与CTL小鼠相比，我们观察到VCD小鼠血清sev中有10个mirna的差异调节。在肝脏中，我们观察到931个基因在VCD + sev中与VCD小鼠相比存在差异表达。有趣的是，VCD处理上调了肝脏中的8条通路，而sev处理下调了肝脏中的8条通路，这表明循环小鼠的sev可以逆转雌激素暂停引起的肝脏变化。Cyp4a12a的表达是男性特异性的，在VCD女性中升高，但sev治疗未使其正常化。我们的研究结果表明，小鼠sev中的miRNA含量受雌激素暂停的调节，与年龄无关。此外，用来自循环小鼠的sev治疗绝经小鼠可以部分逆转肝脏转录组的变化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Molecular and Cellular Endocrinology 医学-内分泌学与代谢

CiteScore

9.00

自引率

2.40%

发文量

174

审稿时长

42 days

期刊介绍： Molecular and Cellular Endocrinology was established in 1974 to meet the demand for integrated publication on all aspects related to the genetic and biochemical effects, synthesis and secretions of extracellular signals (hormones, neurotransmitters, etc.) and to the understanding of cellular regulatory mechanisms involved in hormonal control.