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Androgen receptor signaling and pyrethroids: Potential male infertility consequences

Infertility is a global health concern inflicting a considerable burden on the global economy and a severe socio-psychological impact. Approximately 15% of couples suffer from infertility globally, with a male factor contribution of approximately 50%. However, male infertility remains largely unexpl...

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Autores principales: Sheikh, Ishfaq Ahmad, Beg, Mohd Amin, Hamoda, Taha Abo-AlmagdAbdel-Meguid, Mandourah, Hammam Mahmoud Siraj, Memili, Erdogan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175798/
https://www.ncbi.nlm.nih.gov/pubmed/37187621
http://dx.doi.org/10.3389/fcell.2023.1173575
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author Sheikh, Ishfaq Ahmad
Beg, Mohd Amin
Hamoda, Taha Abo-AlmagdAbdel-Meguid
Mandourah, Hammam Mahmoud Siraj
Memili, Erdogan
author_facet Sheikh, Ishfaq Ahmad
Beg, Mohd Amin
Hamoda, Taha Abo-AlmagdAbdel-Meguid
Mandourah, Hammam Mahmoud Siraj
Memili, Erdogan
author_sort Sheikh, Ishfaq Ahmad
collection PubMed
description Infertility is a global health concern inflicting a considerable burden on the global economy and a severe socio-psychological impact. Approximately 15% of couples suffer from infertility globally, with a male factor contribution of approximately 50%. However, male infertility remains largely unexplored, as the burden of infertility is mostly assigned to female people. Endocrine-disrupting chemicals (EDCs) have been proposed as one of the factors causing male infertility. Pyrethroids represent an important class of EDCs, and numerous studies have associated pyrethroid exposure with impaired male reproductive function and development. Therefore, the present study investigated the potentially toxic effects of two common pyrethroids, cypermethrin and deltamethrin, on androgen receptor (AR) signaling. The structural binding characterization of cypermethrin and deltamethrin against the AR ligand-binding pocket was performed using Schrodinger’s induced fit docking (IFD) approach. Various parameters were estimated, such as binding interactions, binding energy, docking score, and IFD score. Furthermore, the AR native ligand, testosterone, was subjected to similar experiments against the AR ligand-binding pocket. The results revealed commonality in the amino acid-binding interactions and overlap in other structural parameters between the AR native ligand, testosterone, and the ligands, cypermethrin and deltamethrin. The estimated binding energy values of cypermethrin and deltamethrin were very high and close to those calculated for AR native ligand, testosterone. Taken together, the results of this study suggested potential disruption of AR signaling by cypermethrin and deltamethrin, which may result in androgen dysfunction and subsequent male infertility.
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spelling pubmed-101757982023-05-13 Androgen receptor signaling and pyrethroids: Potential male infertility consequences Sheikh, Ishfaq Ahmad Beg, Mohd Amin Hamoda, Taha Abo-AlmagdAbdel-Meguid Mandourah, Hammam Mahmoud Siraj Memili, Erdogan Front Cell Dev Biol Cell and Developmental Biology Infertility is a global health concern inflicting a considerable burden on the global economy and a severe socio-psychological impact. Approximately 15% of couples suffer from infertility globally, with a male factor contribution of approximately 50%. However, male infertility remains largely unexplored, as the burden of infertility is mostly assigned to female people. Endocrine-disrupting chemicals (EDCs) have been proposed as one of the factors causing male infertility. Pyrethroids represent an important class of EDCs, and numerous studies have associated pyrethroid exposure with impaired male reproductive function and development. Therefore, the present study investigated the potentially toxic effects of two common pyrethroids, cypermethrin and deltamethrin, on androgen receptor (AR) signaling. The structural binding characterization of cypermethrin and deltamethrin against the AR ligand-binding pocket was performed using Schrodinger’s induced fit docking (IFD) approach. Various parameters were estimated, such as binding interactions, binding energy, docking score, and IFD score. Furthermore, the AR native ligand, testosterone, was subjected to similar experiments against the AR ligand-binding pocket. The results revealed commonality in the amino acid-binding interactions and overlap in other structural parameters between the AR native ligand, testosterone, and the ligands, cypermethrin and deltamethrin. The estimated binding energy values of cypermethrin and deltamethrin were very high and close to those calculated for AR native ligand, testosterone. Taken together, the results of this study suggested potential disruption of AR signaling by cypermethrin and deltamethrin, which may result in androgen dysfunction and subsequent male infertility. Frontiers Media S.A. 2023-04-28 /pmc/articles/PMC10175798/ /pubmed/37187621 http://dx.doi.org/10.3389/fcell.2023.1173575 Text en Copyright © 2023 Sheikh, Beg, Hamoda, Mandourah and Memili. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Sheikh, Ishfaq Ahmad
Beg, Mohd Amin
Hamoda, Taha Abo-AlmagdAbdel-Meguid
Mandourah, Hammam Mahmoud Siraj
Memili, Erdogan
Androgen receptor signaling and pyrethroids: Potential male infertility consequences
title Androgen receptor signaling and pyrethroids: Potential male infertility consequences
title_full Androgen receptor signaling and pyrethroids: Potential male infertility consequences
title_fullStr Androgen receptor signaling and pyrethroids: Potential male infertility consequences
title_full_unstemmed Androgen receptor signaling and pyrethroids: Potential male infertility consequences
title_short Androgen receptor signaling and pyrethroids: Potential male infertility consequences
title_sort androgen receptor signaling and pyrethroids: potential male infertility consequences
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175798/
https://www.ncbi.nlm.nih.gov/pubmed/37187621
http://dx.doi.org/10.3389/fcell.2023.1173575
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