Aryl hydrocarbon receptor signaling in male fertility: Protective role of resveratrol and disruptive effects of CH223191 in adult male rats.

IF 2 Q2 AGRICULTURE, DAIRY & ANIMAL SCIENCE
Veterinary World Pub Date : 2025-05-01 Epub Date: 2025-05-21 DOI:10.14202/vetworld.2025.1274-1287
Ghadeer Sabah Bustani, Hasan Falah Kashef Alghetaa
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引用次数: 0

Abstract

Background and aim: The aryl hydrocarbon receptor (AhR) plays a pivotal role in spermatogenesis through its regulatory functions in redox balance and gene expression. This study aimed to investigate the effects of resveratrol (RES), a polyphenolic AhR modulator, and CH223191, a selective AhR antagonist, on male reproductive function in rats by assessing sperm quality, oxidative stress, testicular histopathology, and AhR gene expression.

Materials and methods: Forty adult male rats were randomly divided into four groups: (i) Control, (ii) dimethyl sulfoxide (vehicle), (iii) RES (100 mg/kg i.p., twice weekly), and (iv) AhR¯ (CH223191, 10 mg/kg i.p., twice weekly), treated for 60 days. Post-treatment, sperm motility, survival, viability, and DNA fragmentation were evaluated. Total antioxidant capacity (TAC), malondialdehyde (MDA) levels, testicular histopathology, and AhR gene expression quantitative polymerase chain reaction (qPCR) were analyzed.

Results: RES significantly enhanced sperm motility, survival, and viability, reduced DNA fragmentation, and increased TAC while decreasing MDA levels. Histologically, RES preserved normal testicular architecture. In contrast, AhR inhibition through CH223191 led to marked reductions in sperm quality, elevated oxidative stress, increased DNA fragmentation, and severe testicular degeneration. qPCR analysis revealed upregulation of AhR expression in the RES group (fold change: +23.1%) and significant downregulation in the AhR¯ group (fold change: -72.6%), indicating differential modulation of AhR signaling pathways.

Conclusion: RES positively modulates AhR activity, safeguarding testicular structure and enhancing sperm quality through antioxidant and anti-apoptotic mechanisms. Conversely, AhR antagonism disrupts spermatogenesis, underscoring the receptor's essential role in male fertility. These findings suggest the therapeutic potential of AhR-targeting agents like RES in ameliorating male reproductive dysfunctions associated with oxidative stress and xenobiotic exposure.

雄性生殖能力中的芳烃受体信号:白藜芦醇的保护作用和CH223191对成年雄性大鼠的破坏作用。
背景与目的:芳烃受体(aryl hydrocarbon receptor, AhR)通过调控氧化还原平衡和基因表达,在精子发生过程中起着至关重要的作用。本研究旨在通过评估精子质量、氧化应激、睾丸组织病理学和AhR基因表达,探讨多酚类AhR调节剂白藜芦醇(resveratrol, RES)和选择性AhR拮抗剂CH223191对雄性大鼠生殖功能的影响。材料与方法:将40只成年雄性大鼠随机分为4组:(i)对照组,(ii)二甲亚砜(对照剂),(iii) RES (100 mg/kg 1次,每周2次),(iv) AhR¯(CH223191, 10 mg/kg 1次,每周2次),治疗60 d。治疗后,评估精子活力、存活、活力和DNA断裂。分析总抗氧化能力(TAC)、丙二醛(MDA)水平、睾丸组织病理学和AhR基因表达定量聚合酶链反应(qPCR)。结果:RES显著提高精子活力、存活和活力,减少DNA断裂,增加TAC,降低MDA水平。组织学上,RES保留了正常睾丸结构。相反,通过CH223191抑制AhR导致精子质量显著降低、氧化应激升高、DNA断裂增加和严重的睾丸变性。qPCR分析显示,RES组AhR表达上调(翻倍变化:+23.1%),AhR¯组显著下调(翻倍变化:-72.6%),表明AhR信号通路的差异调节。结论:RES正调节AhR活性,通过抗氧化和抗凋亡机制保护睾丸结构,提高精子质量。相反,AhR拮抗剂破坏精子发生,强调受体在男性生育中的重要作用。这些发现表明,像RES这样的ahr靶向药物在改善与氧化应激和外源暴露相关的男性生殖功能障碍方面具有治疗潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Veterinary World
Veterinary World Multiple-
CiteScore
3.60
自引率
12.50%
发文量
317
审稿时长
16 weeks
期刊介绍: Veterinary World publishes high quality papers focusing on Veterinary and Animal Science. The fields of study are bacteriology, parasitology, pathology, virology, immunology, mycology, public health, biotechnology, meat science, fish diseases, nutrition, gynecology, genetics, wildlife, laboratory animals, animal models of human infections, prion diseases and epidemiology. Studies on zoonotic and emerging infections are highly appreciated. Review articles are highly appreciated. All articles published by Veterinary World are made freely and permanently accessible online. All articles to Veterinary World are posted online immediately as they are ready for publication.
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