Deng Juan, Qin Juan, Song Guolin, Li Chenghai, Tang Wentao, Tang Yilin, Xiao Xinfang, Wu Liu, He Sicheng, Zhou Yiqing, Li Junfen, Wang Yan
State Key Laboratory of Ultrasound in Medicine and Engineering Chongqing Medical University Chongqing China.
Chongqing Key Laboratory of Biomedical Engineering Chongqing Medical University Chongqing China.
Bioeng Transl Med. 2024 Dec 17;10(3):e10744. doi: 10.1002/btm2.10744. eCollection 2025 May.
The potential of low-intensity pulsed ultrasound (LIPUS) in regulating ovarian function has been demonstrated; however, there is a lack of scientific evidence regarding the long-term efficacy of LIPUS in treating ovarian injury and understanding its regulatory mechanisms. In this study, 4-vinylcyclohexene diepoxide (VCD) was used to induce ovarian injury in rats, and LIPUS was applied to target the damaged ovarian tissues. The research aimed to investigate the long-term protective effect of LIPUS against ovum toxicity induced by VCD and elucidate the associated molecular mechanisms. During the experiment, HE staining was employed for observing the morphology and structure of the ovary, while protein sequencing was utilized for identifying and confirming the molecular mechanism through which LIPUS restores the damaged ovarian structure. The long-term effectiveness of LIPUS in protecting against ovarian injury was evaluated through ELISA, estrous cycle monitoring, fertility testing, and behavioral analysis. The results indicated that LIPUS effectively restored the structure of damaged ovaries. Both in vivo and in vitro studies revealed that this protective effect may be attributed to LIPUS inhibiting apoptosis of ovarian granulosa cells (GCs) by regulating Daxx-mediated ASK1/JNK signaling pathway. Subsequent functional tests demonstrated significant improvements in sex hormone secretion and regulation of estrous cycle within 6 cycles following LIPUS treatment. Additionally, there was a notable increase in offspring numbers after mating. Behavioral analysis revealed that LIPUS effectively alleviated menopausal symptoms resulting from ovarian injury including mood fluctuations, cognitive behavior changes, and reduced muscle excitability levels. These findings suggest that beneficial effects of LIPUS may help reduce VCD-induced ovarian damage with long-term efficacy.
低强度脉冲超声（LIPUS）调节卵巢功能的潜力已得到证实；然而，关于LIPUS治疗卵巢损伤的长期疗效及其调节机制，缺乏科学证据。在本研究中，使用4-乙烯基环己烯二环氧化物（VCD）诱导大鼠卵巢损伤，并应用LIPUS靶向受损的卵巢组织。该研究旨在探讨LIPUS对VCD诱导的卵子毒性的长期保护作用，并阐明相关的分子机制。实验过程中，采用苏木精-伊红（HE）染色观察卵巢的形态和结构，同时利用蛋白质测序鉴定并确认LIPUS恢复受损卵巢结构的分子机制。通过酶联免疫吸附测定（ELISA）、发情周期监测、生育力测试和行为分析评估LIPUS对卵巢损伤的长期保护效果。结果表明，LIPUS有效恢复了受损卵巢的结构。体内和体外研究均表明，这种保护作用可能归因于LIPUS通过调节Daxx介导的ASK1/JNK信号通路抑制卵巢颗粒细胞（GCs）的凋亡。随后的功能测试表明，LIPUS治疗后6个周期内，性激素分泌和发情周期调节有显著改善。此外，交配后后代数量显著增加。行为分析表明，LIPUS有效缓解了卵巢损伤导致的更年期症状，包括情绪波动、认知行为改变和肌肉兴奋性水平降低。这些发现表明，LIPUS的有益作用可能有助于长期有效减轻VCD诱导的卵巢损伤。
