Aryl Hydrocarbon Receptor Modulation Impacts on the Blood-testis Barrier Integrity via TJP1 Function

Ghadeer Bustani; Hasan Falah K.Aghetaa

doi:10.32598/IJVM.19.3.1005541

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Publication Date

Tue Jul 01 2025

Journal Name

Iranian Journal Of Veterinary Medicine

Volume

19

Issue Number

3

DOI

10.32598/IJVM.19.3.1005541

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Aryl Hydrocarbon Receptor Modulation Impacts on the Blood-testis Barrier Integrity via TJP1 Function

Aryl hydrocarbon receptor (AHR)

CH223191

Resveratrol (RES)

Spermatogenesis

Tight junction protein 1 (TJP1)

Ghadeer Bustani

Hasan Falah K.Aghetaa

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Background: Male infertility is a global concern and it tends to increase due to miscellaneous factors, such as environmental toxins and genetic and lifestyle choices. The aryl hydrocarbon receptor (AHR) has recently attracted attention due to its involvement in male infertility mechanisms and impact on sperm production and function. AHR, a versatile receptor expressed in various tissues, including the testes, regulates the genes involved in spermatogenesis. AHR activation is associated with cell cycle regulation and chromatin condensation during spermatogenesis. Objectives: This study aimed to investigate the influence of AHR activation on blood-testis barrier (BTB) integrity, focusing on the role of tight junction protein-1 (TJP1) and exploring the effects of AHR modulation on spermatogenesis outcomes in adult male rats. Methods: Forty adult male rats were divided into four groups according to their treatment regimens. Briefly, the control group was kept without any treatment, the resveratrol (RES) group received an intraperitoneal (IP) injection of 100 mg/kg every 72 h and the AHR antagonist (AHR‾) group received an IP injection of CH223191 at a dose of 10 mg/kg every 72 h. Finally, the dimethyl sulfoxide (DMSO) group received DMSO which was used as a solvent for preparing RES and CH223191. The study lasted for 60 d to cover the entire spermatogenesis cycle. At the study’s endpoint, sperm chromatin maturity and condensation were evaluated in addition to Tjp1 gene expression in testicular tissue, supported by BTB integrity assessment. Results: The abnormal sperm chromatin maturity (ASCM) and condensation were significantly (P<0.05) higher in AHR‾ compared to all other groups. Tjp1 gene expression was significantly upregulated in the RES group compared to the control and AHR‾ group, which tightened the BTB and maintained the testicular homeostasis for normal spermatogenesis. Conclusion: RES treatment positively influenced sperm chromatin maturity, Tjp1 expression and BTB integrity, suggesting its potential as a protective agent against male reproductive health. Conversely, AHR antagonism leads to compromised sperm chromatin integrity and BTB function, highlighting the critical role of AHR in spermatogenesis and BTB maintenance. These results underscore the importance of AHR modulation in male fertility and provide insights into potential therapeutic interventions.

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Publication Date

Sat Sep 01 2018

Journal Name

Polyhedron

Novel dichloro (bis {2-[1-(4-methylphenyl)-1H-1, 2, 3-triazol-4-yl-κN3] pyridine-κN}) metal (II) coordination compounds of seven transition metals (Mn, Fe, Co, Ni, Cu, Zn and Cd)

The 1

3-dipolar cycloaddition “click” reaction between an azide and an alkyne to give a 1

2

3-triazole was reported by Huisgen in 1961 [1]. In 2002 the Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) to prepare a 1

2

3-triazole was reported [2]

[3]. The existence of relatively basic nitrogen atoms in the 1

2

3-triazole rings

and the possibility of introducing additional donor groups in the substituents (Fig. 1)

made the CuAAC “click” reaction an attractive method to prepare differently substituted 1

2

3-triazoles. These compounds have been used as ligands to coordinate to various metal ions that display a range of applications such as in electrochemical and photochemical studies

in supramolecular chemistry

magnetism

metal-ion sensing and catalysis [4]. The reasons for the success of the “click” reaction

is that it is easy to carry out and is widely applicable. It is not affected by a variety of functional groups

and can be carried out with a variety of Cu(I) catalysts and solvents

including aqueous conditions. The Cu(I) catalysts overcome the high activation energy barrier of the non-catalyzed Huisgen reaction by changing the mechanism of the reaction. A large variety of copper catalysts can be used for the CuAAC reaction

on condition that the maximum concentration of Cu(I) species is generated during the reaction. The pre-catalyst can be a Cu(II) salt (usually CuSO4) together with a reducing agent (often sodium ascorbate) or a Cu(I) compound in the presence of a base or amine ligand and a reducing agent to prevent oxidation to Cu(II). Some strong oxidising cupric salts or complexes such as Cu(OAc)2 also work. The solvent is very flexible from organic to aqueous

with the most commonly used combination water + an alcohol (t-BuOH

MeOH or EtOH). The key role of the solvent or solvent mixture is to solubilize the substrates and Cu(I) catalyst in order to ensure rapid reactions. Such aqueous conditions are very useful for biochemical conjugations

as well as for organic syntheses. We recently reported on the synthesis of a series of differently substituted 1

2

3-triazole chromophores

the substituted 2-(1-phenyl-1H-1

2

3-triazol-4-yl)pyridine ligands [5]

see Fig. 2 middle

with substituents R = H (L1)

CH3 (L2)

OCH3 (L3)

COOH

F

Cl

CN

CF3

O(CH2)3CH3 and N(CH3)2. These versatile ligands were found to coordinate to various first row transition metals

such as manganese

cobalt and nickel [6]. Here we extend the series to include more first row transition metal(II) coordination compounds

iron

copper and zinc

as well as a second row transition metal(II) coordination compound

cadmium

containing the 2-(1-(4-methyl-phenyl)-1H-1

2

3-triazol-1-yl)pyridine chromophore (Fig. 2 right with R = CH3). This series of seven novel coordination compounds is the first series of pyridyl-triazole based transition metal coordination compounds where seven different transition metals are coordinated to the same 1

2

3-triazole chromophore

namely 2-(1-(4-methyl-phenyl)-1H-1

2

3-triazol-1-yl)pyridine.

Kinaan M

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Publication Date

Sun Dec 07 2014

Journal Name

Baghdad Science Journal

Synthesis, Characterization and Stability Study of V(IV), Zr(IV), Rh(III), Pd(II), Cd(II) and Hg(II) Complexes with Pyrazol Derivative

In this work lactone (1) was prepared from the reaction of p-nitro phenyl hydrazine with ethylacetoacetate

which upon treatment with benzoyl chloride afforded the lactame (2). The reaction of (2) with 2-amino phenol produced a new Schiff base (L) in good yield. Complexes of V(IV)

Zr(IV)

Rh(III)

Pd(II)

Cd(II) and Hg(II) with the new Schiff base (L) have been prepared. The compounds (1

2) were characterized by FT-IR and UV spectroscopy

as well as characterizing ligand (L) by the same techniques with elemental analysis (C.H.N) and (1H-NMR). The prepared complexes were identified and their structural geometries were suggested by using elemental analysis (C.H.N)

flame atomic absorption technique

FT-IR and UV-Vis spectroscopy

in addition to magnetic susceptibility and conductivity measurements. Metal to ligand [M:L] ratio was obtained for all complexes in ethanol using molar ratio method

which gave comparable results with those obtained for the solid complexes. As well as the appa

Sinan M.

Enaam M.

Maysoon A

Sarab M

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In this work lactone (1) was prepared from the reaction of p-nitro phenyl hydrazine with ethylacetoacetate, which upon treatment with benzoyl chloride afforded the lactame (2). The reaction of (2) with 2-amino phenol produced a new Schiff base (L) in good yield. Complexes of V(IV), Zr(IV), Rh(III), Pd(II), Cd(II) and Hg(II) with the new Schiff base (L) have been prepared. The compounds (1, 2) were characterized by FT-IR and UV spectroscopy, as well as characterizing ligand (L) by the same techniques with elemental analysis (C.H.N) and (1H-NMR). The prepared complexes were identified and their structural geometries were suggested by using elemental analysis (C.H.N), flame atomic absorption technique, FT-IR and UV-Vis spectroscopy, in additio

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