Effects of Wuzi Yanzong Pill on Mitochondrial Homeostasis and the cGAS-STING Signaling Pathway in Rats Under Testicular Heat Stress

IF 2 4区 医学 Q3 ANDROLOGY
Andrologia Pub Date : 2025-09-05 DOI:10.1155/and/1637113
Chenxiao Liu, Zuomei Zeng, Xinyue Wang, Yichen Wang, Di Deng, Jian Guo
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Abstract

The incidence of male infertility has remained notably high in recent years, with testicular inflammation being a major contributing factor. Testicular heat stress (THS) is a common inducer of testicular inflammation. Testicular tissue is rich in mitochondria, and disruptions in mitochondrial homeostasis may play a key role in driving inflammation. Wuzi Yanzong Pill (WZYZ Pill), a traditional Chinese medicine (TCM) formula, has long been used in treating male infertility and may inhibit testicular inflammation caused by heat stress. In this study, a rat model of THS was established, and WZYZ Pill was administered at different doses. The effects of WZYZ Pill on sperm parameters, testicular histology, and the secretion of inflammatory factors were assessed. The study also examined the link between mitochondrial imbalance and inflammation, aiming to clarify whether the WZYZ Pill interferes with this pathway. Western blotting, immunohistochemistry, and real-time PCR (RT-PCR) were used to assess mitochondrial DNA (mtDNA) leakage and the expression of key regulators of mitochondrial homeostasis and the cyclic GMP–AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway. The results showed that heat stress disrupted mitochondrial homeostasis, leading to mtDNA leakage and activation of the cGAS-STING pathway, which contributed to testicular inflammation. WZYZ Pill significantly improved mitochondrial homeostasis, reduced mtDNA leakage, suppressed the expression of cGAS-STING-related molecules, and decreased the secretion of inflammatory factors in testicular tissue, ultimately alleviating the adverse effects of heat stress on both testicular structure and sperm production.

Abstract Image

五子炎宗丸对睾丸热应激大鼠线粒体稳态及cGAS-STING信号通路的影响
近年来,男性不育症的发病率仍然很高,睾丸炎症是一个主要因素。睾丸热应激是睾丸炎症的常见诱因。睾丸组织富含线粒体,线粒体稳态的破坏可能在驱动炎症中起关键作用。五子炎宗丸(WZYZ丸)是一种中药配方,长期用于治疗男性不育症,可能抑制由热应激引起的睾丸炎症。本研究建立三手弓形虫大鼠模型,给药不同剂量的WZYZ丸。观察WZYZ丸对大鼠精子参数、睾丸组织学及炎性因子分泌的影响。该研究还检查了线粒体失衡和炎症之间的联系,旨在澄清WZYZ药丸是否干扰了这一途径。采用Western blotting、免疫组织化学和实时荧光定量PCR (RT-PCR)检测线粒体DNA (mtDNA)渗漏、线粒体稳态关键调控因子和环GMP-AMP合成酶(cGAS)-干扰素基因(STING)信号通路刺激因子的表达。结果表明,热应激破坏线粒体稳态,导致mtDNA泄漏和cGAS-STING通路激活,从而导致睾丸炎症。WZYZ丸显著改善线粒体稳态,减少mtDNA泄漏,抑制cgas - sting相关分子的表达,降低睾丸组织炎症因子的分泌,最终缓解热应激对睾丸结构和精子产生的不利影响。
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来源期刊
Andrologia
Andrologia 医学-男科学
CiteScore
5.60
自引率
8.30%
发文量
292
审稿时长
6 months
期刊介绍: Andrologia provides an international forum for original papers on the current clinical, morphological, biochemical, and experimental status of organic male infertility and sexual disorders in men. The articles inform on the whole process of advances in andrology (including the aging male), from fundamental research to therapeutic developments worldwide. First published in 1969 and the first international journal of andrology, it is a well established journal in this expanding area of reproductive medicine.
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