Jialing Li, Hua Guo, Miaomiao Tian, Feimiao Wang, Jinmei Gao, Lu Wang, Jie Ma, Rong Hu
{"title":"外泌体衍生的lncRNA LIPE-AS1通过miR-330-5p/HDAC3轴促进卵母细胞成熟并改善卵巢储备减少","authors":"Jialing Li, Hua Guo, Miaomiao Tian, Feimiao Wang, Jinmei Gao, Lu Wang, Jie Ma, Rong Hu","doi":"10.1002/jbt.70519","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Diminished ovarian reserve (DOR) is a multifactorial gynecological disorder that has emerged as a significant global health challenge. Currently, there are no effective preventive or therapeutic strategies for DOR. Exosome-derived long non-coding RNAs (lncRNA) in follicular fluid (FF) plays a crucial role in follicular development. We identified exosome-derived lncRNA LIPE-AS1 from the FF of DOR patients, which regulates histone deacetylase 3 (HDAC3) expression by competitively binding to miR-330-5p. Exosomes, as nanosized membrane vesicles, can deliver therapeutic agents in a targeted manner through ligand modification. In this study, we employed engineered exosomes combined with lncRNA for ovary-targeted therapy of DOR. First, we elucidated the role of lncRNA LIPE-AS1 in the pathogenesis of DOR. Next, we generated exosomes with high LIPE-AS1 expression (Exo-LIPE-AS1) using 293 T cells. Co-culture of Exo-LIPE-AS1 with oocytes from DOR models enhanced oocyte maturation and improve oocyte quality in vitro. Finally, we developed FSHβ-modified, LIPE-AS1-loaded exosomes (Exo<sub>FSHβ</sub>-LIPE-AS1), which demonstrated enhanced ovarian delivery efficiency in vivo. Consequently, Exo<sub>FSHβ</sub>-LIPE-AS1improved fertility outcomes in DOR models. Our findings demonstrate that exosomes serve as effective targeted vehicles for lncRNA LIPE-AS1, offering potential preventive and therapeutic benefits for DOR.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exosome-Derived lncRNA LIPE-AS1 Enhances Oocytes Maturation and Ameliorates Diminished Ovarian Reserve via the miR-330-5p/HDAC3 Axis\",\"authors\":\"Jialing Li, Hua Guo, Miaomiao Tian, Feimiao Wang, Jinmei Gao, Lu Wang, Jie Ma, Rong Hu\",\"doi\":\"10.1002/jbt.70519\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Diminished ovarian reserve (DOR) is a multifactorial gynecological disorder that has emerged as a significant global health challenge. Currently, there are no effective preventive or therapeutic strategies for DOR. Exosome-derived long non-coding RNAs (lncRNA) in follicular fluid (FF) plays a crucial role in follicular development. We identified exosome-derived lncRNA LIPE-AS1 from the FF of DOR patients, which regulates histone deacetylase 3 (HDAC3) expression by competitively binding to miR-330-5p. Exosomes, as nanosized membrane vesicles, can deliver therapeutic agents in a targeted manner through ligand modification. In this study, we employed engineered exosomes combined with lncRNA for ovary-targeted therapy of DOR. First, we elucidated the role of lncRNA LIPE-AS1 in the pathogenesis of DOR. Next, we generated exosomes with high LIPE-AS1 expression (Exo-LIPE-AS1) using 293 T cells. Co-culture of Exo-LIPE-AS1 with oocytes from DOR models enhanced oocyte maturation and improve oocyte quality in vitro. Finally, we developed FSHβ-modified, LIPE-AS1-loaded exosomes (Exo<sub>FSHβ</sub>-LIPE-AS1), which demonstrated enhanced ovarian delivery efficiency in vivo. Consequently, Exo<sub>FSHβ</sub>-LIPE-AS1improved fertility outcomes in DOR models. Our findings demonstrate that exosomes serve as effective targeted vehicles for lncRNA LIPE-AS1, offering potential preventive and therapeutic benefits for DOR.</p></div>\",\"PeriodicalId\":15151,\"journal\":{\"name\":\"Journal of Biochemical and Molecular Toxicology\",\"volume\":\"39 10\",\"pages\":\"\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-09-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biochemical and Molecular Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70519\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biochemical and Molecular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70519","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Exosome-Derived lncRNA LIPE-AS1 Enhances Oocytes Maturation and Ameliorates Diminished Ovarian Reserve via the miR-330-5p/HDAC3 Axis
Diminished ovarian reserve (DOR) is a multifactorial gynecological disorder that has emerged as a significant global health challenge. Currently, there are no effective preventive or therapeutic strategies for DOR. Exosome-derived long non-coding RNAs (lncRNA) in follicular fluid (FF) plays a crucial role in follicular development. We identified exosome-derived lncRNA LIPE-AS1 from the FF of DOR patients, which regulates histone deacetylase 3 (HDAC3) expression by competitively binding to miR-330-5p. Exosomes, as nanosized membrane vesicles, can deliver therapeutic agents in a targeted manner through ligand modification. In this study, we employed engineered exosomes combined with lncRNA for ovary-targeted therapy of DOR. First, we elucidated the role of lncRNA LIPE-AS1 in the pathogenesis of DOR. Next, we generated exosomes with high LIPE-AS1 expression (Exo-LIPE-AS1) using 293 T cells. Co-culture of Exo-LIPE-AS1 with oocytes from DOR models enhanced oocyte maturation and improve oocyte quality in vitro. Finally, we developed FSHβ-modified, LIPE-AS1-loaded exosomes (ExoFSHβ-LIPE-AS1), which demonstrated enhanced ovarian delivery efficiency in vivo. Consequently, ExoFSHβ-LIPE-AS1improved fertility outcomes in DOR models. Our findings demonstrate that exosomes serve as effective targeted vehicles for lncRNA LIPE-AS1, offering potential preventive and therapeutic benefits for DOR.
期刊介绍：
The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
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