The dose-dependent dual effects of alpha-ketoglutarate (AKG) on cumulus oocyte complexes during in vitro maturation.

IF 8.2 2区生物学 Q1 CELL BIOLOGY

Cell Communication and Signaling Pub Date : 2024-10-03 DOI:10.1186/s12964-024-01827-z

Yunjie Liu, Xin Xiao, Likai Wang, Yao Fu, Songyang Yao, Xuening Liu, Boda Chen, Jiarui Gao, Yaying Zhai, Zixia Shen, Laiqing Yan, Yiwei Wang, Pengyun Ji, Bingyuan Wang, Guoshi Liu

{"title":"The dose-dependent dual effects of alpha-ketoglutarate (AKG) on cumulus oocyte complexes during in vitro maturation.","authors":"Yunjie Liu, Xin Xiao, Likai Wang, Yao Fu, Songyang Yao, Xuening Liu, Boda Chen, Jiarui Gao, Yaying Zhai, Zixia Shen, Laiqing Yan, Yiwei Wang, Pengyun Ji, Bingyuan Wang, Guoshi Liu","doi":"10.1186/s12964-024-01827-z","DOIUrl":null,"url":null,"abstract":"<p><p>In this study, we reported for the first time the dose-dependent dual effects of Alpha-Ketoglutarate (AKG) on cumulus oocyte complexes (COCs) during in vitro maturation (IVM). AKG at appropriate concentration (30 µM) has beneficial effects on IVM. This includes improved cumulus expansion, oocyte quality, and embryo development. These effects are mediated through multiple underlying mechanisms. AKG reduced the excessive accumulation of reactive oxygen species (ROS) in cumulus cells, reduced the consumption of GSH and NADPH. Cumulus GSH and NADPH were transported to oocytes via gap junctions, thereby reducing the oxidative stress, apoptosis and maintaining the redox balance in oocytes. In addition, AKG improved the mitochondrial function by regulating the mitochondrial complex 1 related gene expression in oocytes to maintain mitochondrial membrane potential and ATP production. On the other hand, oocyte generated GDF9 could also be transported to cumulus cells to promote cumulus expansion. Conversely, a high concentration of AKG (750 µM) exerted adverse effects on IVM and suppressed the cumulus expansion as well as reduced the oocyte quality. The suppression of the cumulus expansion caused by high concentration of AKG could be rescued with GDF9 supplementation in COCs, indicating the critical role of GDF9 in IVM. The results provide valuable information on the variable effects of AKG at different concentrations on reproductive physiology.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"472"},"PeriodicalIF":8.2000,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448289/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Communication and Signaling","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s12964-024-01827-z","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

In this study, we reported for the first time the dose-dependent dual effects of Alpha-Ketoglutarate (AKG) on cumulus oocyte complexes (COCs) during in vitro maturation (IVM). AKG at appropriate concentration (30 µM) has beneficial effects on IVM. This includes improved cumulus expansion, oocyte quality, and embryo development. These effects are mediated through multiple underlying mechanisms. AKG reduced the excessive accumulation of reactive oxygen species (ROS) in cumulus cells, reduced the consumption of GSH and NADPH. Cumulus GSH and NADPH were transported to oocytes via gap junctions, thereby reducing the oxidative stress, apoptosis and maintaining the redox balance in oocytes. In addition, AKG improved the mitochondrial function by regulating the mitochondrial complex 1 related gene expression in oocytes to maintain mitochondrial membrane potential and ATP production. On the other hand, oocyte generated GDF9 could also be transported to cumulus cells to promote cumulus expansion. Conversely, a high concentration of AKG (750 µM) exerted adverse effects on IVM and suppressed the cumulus expansion as well as reduced the oocyte quality. The suppression of the cumulus expansion caused by high concentration of AKG could be rescued with GDF9 supplementation in COCs, indicating the critical role of GDF9 in IVM. The results provide valuable information on the variable effects of AKG at different concentrations on reproductive physiology.

查看原文本刊更多论文

体外成熟过程中，α-酮戊二酸（AKG）对积卵母细胞复合体具有剂量依赖性的双重影响。

在这项研究中，我们首次报道了α-酮戊二酸（AKG）在体外成熟（IVM）过程中对积层卵母细胞复合体（COCs）的剂量依赖性双重效应。适当浓度（30 µM）的 AKG 对 IVM 有益。这包括改善积腺扩张、卵母细胞质量和胚胎发育。这些作用是通过多种基本机制介导的。AKG 可减少积层细胞中活性氧（ROS）的过度积累，减少 GSH 和 NADPH 的消耗。积液中的 GSH 和 NADPH 通过间隙连接被运输到卵母细胞中，从而减少了氧化应激和细胞凋亡，维持了卵母细胞中的氧化还原平衡。此外，AKG 还通过调节卵母细胞中线粒体复合物 1 相关基因的表达来改善线粒体功能，从而维持线粒体膜电位和 ATP 的产生。另一方面，卵母细胞产生的 GDF9 还能被转运到精原细胞，促进精原细胞的扩增。相反，高浓度的 AKG（750 µM）会对 IVM 产生不利影响，抑制精母细胞的扩增，并降低卵母细胞的质量。补充 GDF9 后，COCs 中高浓度 AKG 对精母细胞扩增的抑制作用得以缓解，这表明 GDF9 在 IVM 中起着关键作用。这些结果为研究不同浓度的 AKG 对生殖生理的不同影响提供了有价值的信息。

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

Cell Communication and Signaling CELL BIOLOGY-

CiteScore

11.00

自引率

0.00%

发文量

180

期刊介绍： Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.