Zhu Yaoyao, Lu Ge, Li Weixin, Su Chenchen, Du Pengfei, Wang Shuyou, Yang Li, Xu Huanfang, Fang Yigong, Song Xiaojing
Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.
Front Endocrinol (Lausanne). 2025 May 8;16:1579031. doi: 10.3389/fendo.2025.1579031. eCollection 2025.
Age-related ovarian dysfunction, characterized by declining follicular reserve and hormonal imbalance, poses a significant challenge in reproductive endocrinology, severely compromising fertility and quality of life. Although acupuncture at conception vessel acupoints is an effective therapeutic approach for managing ovarian dysfunction, the biological underpinnings bridging peripheral stimulation to systemic endocrine regulation remain elusive. Emerging evidence has highlighted interstitial fluid (ISF) dynamics as a potential mediator of mechanotransduction. However, it remains to be elucidated whether ISF transport in the linea alba (abdominal trajectory of conception vessel) influences ovarian function, and whether acupuncture at conception vessel acupoints exerts its therapeutic effects through ISF-mediated substance transport along the linea alba.
We used fluorescence imaging to observe ISF migration patterns in the linea alba of rats, where conception vessel acupoints are located. In addition, we investigated the ovarian functional changes post-ISF obstruction and evaluated the therapeutic effects of acupuncture on ovarian dysfunction in aged rats, both in unblocked and ISF-blockade conditions.
Fluorescence imaging revealed ISF transport along the linea alba, with tracers migrating linearly, a pattern abolished by surgical blockade. Abnormal ISF transport in the linea alba may affect the homeostasis of reproductive hormone levels. Serum follicle-stimulating and luteinizing hormones increased while E decreased, accompanied by follicular depletion and hypothalamic-pituitary-ovarian axis dysregulation. Acupuncture at CV4 attenuated ovarian aging, elevating developmental follicle counts, reducing granulosa cell apoptosis, and restoring hypothalamic-pituitary-ovarian axis function. Crucially, these therapeutic benefits were nullified under ISF blockade conditions.
Our results suggest that ISF transport in the linea alba may serve as an important mechanistic pathway bridging acupuncture stimulation to ovarian regulation. Our study not only provides a mechanistic basis for the clinical efficacy of acupuncture in treating ovarian disorders but also identifies ISF dynamics as a novel therapeutic target in age-related ovarian dysfunction.
与年龄相关的卵巢功能障碍,其特征为卵泡储备减少和激素失衡,这在生殖内分泌学中构成了重大挑战,严重影响生育能力和生活质量。尽管针刺任脉穴位是治疗卵巢功能障碍的有效方法,但其将外周刺激与全身内分泌调节联系起来的生物学基础仍不清楚。新出现的证据强调组织间液(ISF)动态变化是机械转导的潜在介质。然而,任脉腹部循行路线(白线)中的ISF运输是否影响卵巢功能,以及针刺任脉穴位是否通过ISF介导的物质沿白线运输发挥治疗作用,仍有待阐明。
我们使用荧光成像观察大鼠白线(任脉穴位所在部位)中ISF的迁移模式。此外,我们研究了ISF阻塞后卵巢功能的变化,并评估了针刺对老年大鼠卵巢功能障碍的治疗效果,包括未阻塞和ISF阻断条件下的情况。
荧光成像显示ISF沿白线运输,示踪剂呈线性迁移,手术阻断后这种模式消失。白线中异常的ISF运输可能影响生殖激素水平的稳态。血清促卵泡生成素和促黄体生成素升高而雌激素降低,同时伴有卵泡耗竭和下丘脑-垂体-卵巢轴失调。针刺关元穴可减轻卵巢衰老,增加发育卵泡数量,减少颗粒细胞凋亡,并恢复下丘脑-垂体-卵巢轴功能。至关重要的是,在ISF阻断条件下,这些治疗益处消失。
我们的结果表明,白线中的ISF运输可能是将针刺刺激与卵巢调节联系起来的重要机制途径。我们的研究不仅为针刺治疗卵巢疾病的临床疗效提供了机制基础,还确定ISF动态变化是与年龄相关的卵巢功能障碍的新治疗靶点。