In Vitro Exposure to the Endocrine-Disrupting Chemical Climbazole Impairs Human Sperm Motility, Hormonal Signalling, and Mitochondrial Activity

This study explores the endocrine-disrupting effects of climbazole (CBZ), an environmental and lifestyle stressor, on male fertility. The impact of CBZ on sperm vitality, motility, and molecular pathways related to hormone receptors and apoptosis was evaluated, in non-capacitated and capacitated con...

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Main Authors: Eugenia Annunzi, Francesca Paola Luongo, Francesca Girolamo, Rosetta Ponchia, Sofia Passaponti, Paola Piomboni, Alice Luddi
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/6/427
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author Eugenia Annunzi
Francesca Paola Luongo
Francesca Girolamo
Rosetta Ponchia
Sofia Passaponti
Paola Piomboni
Alice Luddi
author_facet Eugenia Annunzi
Francesca Paola Luongo
Francesca Girolamo
Rosetta Ponchia
Sofia Passaponti
Paola Piomboni
Alice Luddi
author_sort Eugenia Annunzi
collection DOAJ
description This study explores the endocrine-disrupting effects of climbazole (CBZ), an environmental and lifestyle stressor, on male fertility. The impact of CBZ on sperm vitality, motility, and molecular pathways related to hormone receptors and apoptosis was evaluated, in non-capacitated and capacitated conditions. Gene expression of key components, including hormone receptors (<i>ESR1</i>, <i>ESR2</i>, <i>FSHR</i>, <i>AR</i>), apoptosis-related genes (<i>BAX</i>, <i>BCL2</i>), and <i>COX4l1</i> (involved in mitochondrial function), was analyzed. Protein tyrosine phosphorylation, a marker of capacitation, was also examined using immunofluorescence and Western blot analysis. We demonstrated that CBZ significantly reduced sperm vitality at concentrations above 25 µM and motility at 1 and 10 µM in non-capacitated and capacitated conditions. Changes in tyrosine phosphorylation patterns were also observed. Gene expression analysis revealed an upregulation of <i>ESR1</i>, <i>ESR2</i>, <i>FSHR</i>, and <i>BAX</i>, while <i>AR</i> and <i>COX4l1</i> expression were downregulated. These findings offer new insights into the potential endocrine-disrupting and cytotoxic effects of CBZ, highlighting its potential role in compromising male reproductive health.
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spelling doaj-art-2de86dcec479464fba2f5e9a68a935d72025-08-20T03:43:11ZengMDPI AGCells2073-44092025-03-0114642710.3390/cells14060427In Vitro Exposure to the Endocrine-Disrupting Chemical Climbazole Impairs Human Sperm Motility, Hormonal Signalling, and Mitochondrial ActivityEugenia Annunzi0Francesca Paola Luongo1Francesca Girolamo2Rosetta Ponchia3Sofia Passaponti4Paola Piomboni5Alice Luddi6Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, 53100 Siena, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, 53100 Siena, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, 53100 Siena, ItalyDepartment of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, 53100 Siena, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, 53100 Siena, ItalyThis study explores the endocrine-disrupting effects of climbazole (CBZ), an environmental and lifestyle stressor, on male fertility. The impact of CBZ on sperm vitality, motility, and molecular pathways related to hormone receptors and apoptosis was evaluated, in non-capacitated and capacitated conditions. Gene expression of key components, including hormone receptors (<i>ESR1</i>, <i>ESR2</i>, <i>FSHR</i>, <i>AR</i>), apoptosis-related genes (<i>BAX</i>, <i>BCL2</i>), and <i>COX4l1</i> (involved in mitochondrial function), was analyzed. Protein tyrosine phosphorylation, a marker of capacitation, was also examined using immunofluorescence and Western blot analysis. We demonstrated that CBZ significantly reduced sperm vitality at concentrations above 25 µM and motility at 1 and 10 µM in non-capacitated and capacitated conditions. Changes in tyrosine phosphorylation patterns were also observed. Gene expression analysis revealed an upregulation of <i>ESR1</i>, <i>ESR2</i>, <i>FSHR</i>, and <i>BAX</i>, while <i>AR</i> and <i>COX4l1</i> expression were downregulated. These findings offer new insights into the potential endocrine-disrupting and cytotoxic effects of CBZ, highlighting its potential role in compromising male reproductive health.https://www.mdpi.com/2073-4409/14/6/427endocrine-disrupting chemicals (EDCs)male fertilityclimbazole (CBZ)semen qualityoxidative stress
spellingShingle Eugenia Annunzi
Francesca Paola Luongo
Francesca Girolamo
Rosetta Ponchia
Sofia Passaponti
Paola Piomboni
Alice Luddi
In Vitro Exposure to the Endocrine-Disrupting Chemical Climbazole Impairs Human Sperm Motility, Hormonal Signalling, and Mitochondrial Activity
Cells
endocrine-disrupting chemicals (EDCs)
male fertility
climbazole (CBZ)
semen quality
oxidative stress
title In Vitro Exposure to the Endocrine-Disrupting Chemical Climbazole Impairs Human Sperm Motility, Hormonal Signalling, and Mitochondrial Activity
title_full In Vitro Exposure to the Endocrine-Disrupting Chemical Climbazole Impairs Human Sperm Motility, Hormonal Signalling, and Mitochondrial Activity
title_fullStr In Vitro Exposure to the Endocrine-Disrupting Chemical Climbazole Impairs Human Sperm Motility, Hormonal Signalling, and Mitochondrial Activity
title_full_unstemmed In Vitro Exposure to the Endocrine-Disrupting Chemical Climbazole Impairs Human Sperm Motility, Hormonal Signalling, and Mitochondrial Activity
title_short In Vitro Exposure to the Endocrine-Disrupting Chemical Climbazole Impairs Human Sperm Motility, Hormonal Signalling, and Mitochondrial Activity
title_sort in vitro exposure to the endocrine disrupting chemical climbazole impairs human sperm motility hormonal signalling and mitochondrial activity
topic endocrine-disrupting chemicals (EDCs)
male fertility
climbazole (CBZ)
semen quality
oxidative stress
url https://www.mdpi.com/2073-4409/14/6/427
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