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
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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.
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.