Melatonin Protects against LPS-Induced Mitochondrial Dyshomeostasis and Ovarian Damage through JNK Signaling Pathway in Mouse Ovary.

IF 2.5 3区 医学 Q2 OBSTETRICS & GYNECOLOGY
Reproductive Sciences Pub Date : 2025-09-01 Epub Date: 2025-08-12 DOI:10.1007/s43032-025-01954-z
Ling-Ge Shi, Si-Min Ding, Tong-Kun Guo, Peng Chen, Shuang-Shuang Cui, Zhuo-Nan Yang, Mengyao Wang, Rui Wang, Dongmei Ji, Tao Zhang, Dan Liang, Lili Wang, Yunxia Cao, Yajing Liu
{"title":"Melatonin Protects against LPS-Induced Mitochondrial Dyshomeostasis and Ovarian Damage through JNK Signaling Pathway in Mouse Ovary.","authors":"Ling-Ge Shi, Si-Min Ding, Tong-Kun Guo, Peng Chen, Shuang-Shuang Cui, Zhuo-Nan Yang, Mengyao Wang, Rui Wang, Dongmei Ji, Tao Zhang, Dan Liang, Lili Wang, Yunxia Cao, Yajing Liu","doi":"10.1007/s43032-025-01954-z","DOIUrl":null,"url":null,"abstract":"<p><p>Both mitochondrial dysfunction and inflammation are closely associated with the pathogenesis of diminished ovarian reserve (DOR). While melatonin (MT) is known to protect against ovarian injury, its precise mechanism in counteracting lipopolysaccharide (LPS)-induced mitochondrial dysfunction and ovarian reserve impairment remains unclear. This study aimed to explore the effects and underlying mechanisms of MT on LPS-induced ovarian reserve dysfunction. Follicle development in mouse models was assessed using HE staining and follicle counting. Immunofluorescence, Western blotting, and quantitative real-time PCR were employed to investigate the biological mechanisms by which MT protects the ovary. The levels of reactive oxygen species (ROS) and mitochondrial function in KGN cells were evaluated using H2DCFDA and TMRE staining. The findings revealed that LPS stimulation led to reduced expression of anti-Mullerian hormone (AMH) and growth differentiation factor 9 (GDF9), indicating impaired ovarian function. Treatment with MT countered these effects. Immunofluorescence analysis demonstrated that MT alleviated LPS-induced follicular depletion and modulated the expression levels of mitochondrial dynamics-related proteins OPA1 and DRP1. Additionally, LPS exposure induced excessive autophagy, elevated ROS levels, and heightened inflammation but did not significantly affect cell cycle progression or apoptosis. Notably, MT rescued the suppression of the JNK pathway caused by LPS stimulation. In summary, our results indicate that MT effectively restores the balance between mitochondrial fusion and fission, enhances ovarian reserve function via activation of the JNK signaling pathway, suppresses inflammation and autophagy, and ultimately improves overall ovarian function.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3154-3165"},"PeriodicalIF":2.5000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive Sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s43032-025-01954-z","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/12 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Both mitochondrial dysfunction and inflammation are closely associated with the pathogenesis of diminished ovarian reserve (DOR). While melatonin (MT) is known to protect against ovarian injury, its precise mechanism in counteracting lipopolysaccharide (LPS)-induced mitochondrial dysfunction and ovarian reserve impairment remains unclear. This study aimed to explore the effects and underlying mechanisms of MT on LPS-induced ovarian reserve dysfunction. Follicle development in mouse models was assessed using HE staining and follicle counting. Immunofluorescence, Western blotting, and quantitative real-time PCR were employed to investigate the biological mechanisms by which MT protects the ovary. The levels of reactive oxygen species (ROS) and mitochondrial function in KGN cells were evaluated using H2DCFDA and TMRE staining. The findings revealed that LPS stimulation led to reduced expression of anti-Mullerian hormone (AMH) and growth differentiation factor 9 (GDF9), indicating impaired ovarian function. Treatment with MT countered these effects. Immunofluorescence analysis demonstrated that MT alleviated LPS-induced follicular depletion and modulated the expression levels of mitochondrial dynamics-related proteins OPA1 and DRP1. Additionally, LPS exposure induced excessive autophagy, elevated ROS levels, and heightened inflammation but did not significantly affect cell cycle progression or apoptosis. Notably, MT rescued the suppression of the JNK pathway caused by LPS stimulation. In summary, our results indicate that MT effectively restores the balance between mitochondrial fusion and fission, enhances ovarian reserve function via activation of the JNK signaling pathway, suppresses inflammation and autophagy, and ultimately improves overall ovarian function.

褪黑素通过JNK信号通路保护小鼠卵巢免受lps诱导的线粒体失衡和卵巢损伤。
线粒体功能障碍和炎症与卵巢储备功能减退(DOR)的发病机制密切相关。虽然褪黑素(MT)已知可以防止卵巢损伤,但其对抗脂多糖(LPS)诱导的线粒体功能障碍和卵巢储备损伤的确切机制尚不清楚。本研究旨在探讨MT对lps诱导的卵巢储备功能障碍的影响及其机制。利用HE染色和卵泡计数评估小鼠模型的卵泡发育。采用免疫荧光、Western blotting、实时荧光定量PCR等方法研究MT保护卵巢的生物学机制。采用H2DCFDA和TMRE染色评价KGN细胞的活性氧(ROS)水平和线粒体功能。结果显示,LPS刺激导致抗苗勒管激素(AMH)和生长分化因子9 (GDF9)表达降低,提示卵巢功能受损。MT治疗抵消了这些影响。免疫荧光分析显示,MT减轻了lps诱导的卵泡衰竭,并调节了线粒体动力学相关蛋白OPA1和DRP1的表达水平。此外,LPS暴露诱导过度自噬、ROS水平升高和炎症加剧,但对细胞周期进展或凋亡没有显著影响。值得注意的是,MT恢复了LPS刺激引起的JNK通路的抑制。综上所述,我们的研究结果表明,MT有效地恢复了线粒体融合和裂变之间的平衡,通过激活JNK信号通路增强卵巢储备功能,抑制炎症和自噬,最终改善卵巢整体功能。
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
Reproductive Sciences
Reproductive Sciences 医学-妇产科学
CiteScore
5.50
自引率
3.40%
发文量
322
审稿时长
4-8 weeks
期刊介绍: Reproductive Sciences (RS) is a peer-reviewed, monthly journal publishing original research and reviews in obstetrics and gynecology. RS is multi-disciplinary and includes research in basic reproductive biology and medicine, maternal-fetal medicine, obstetrics, gynecology, reproductive endocrinology, urogynecology, fertility/infertility, embryology, gynecologic/reproductive oncology, developmental biology, stem cell research, molecular/cellular biology and other related fields.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信