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

Vet World Vol.18 May-2025 Article - 19

Research Article

Veterinary World, 18(5): 1274-1287

https://doi.org/10.14202/vetworld.2025.1274-1287

Ghadeer Sabah Bustani^1,2

and Hasan Falah Kashef Alghetaa¹

1. Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Baghdad, Baghdad, Iraq.

2. Department of Anesthesia, Faculty of Medical Technologies, The Islamic University, Najaf, Iraq.

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.

Keywords: antioxidant capacity, aryl hydrocarbon receptor, resveratrol, CH223191, oxidative stress, sperm DNA fragmentation, spermatogenesis.

How to cite this article: Bustani GS, and Alghetaa HFK (2025) Aryl hydrocarbon receptor signaling in male fertility: Protective role of resveratrol and disruptive effects of CH223191 in adult male rats, Veterinary World, 18(4): 1274–1287.

Received: 16-02-2025 Accepted: 17-04-2025 Published online: 21-05-2025

Corresponding author: Hasan Falah Kashef Alghetaa E-mail: kashifalkitaa@covm.uobaghdad.edu.iq

DOI: 10.14202/vetworld.2025.1274-1287

Copyright: Bustani, et al. This article is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.