Nickel oxide nanoparticles exposure as a risk factor for male infertility: “In vitro” effects on porcine pre-pubertal Sertoli cells

Lately, nickel oxide nanoparticles (NiO NPs) have been employed in different industrial and biomedical fields. Several studies have reported that NiO NPs may affect the development of reproductive organs inducing oxidative stress and, resulting in male infertility. We investigated the in vitro effec...

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Main Authors: Iva Arato, Stefano Giovagnoli, Alessandro Di Michele, Catia Bellucci, Cinzia Lilli, Maria Chiara Aglietti, Desirée Bartolini, Angela Gambelunghe, Giacomo Muzi, Mario Calvitti, Elena Eugeni, Francesco Gaggia, Tiziano Baroni, Francesca Mancuso, Giovanni Luca
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2023.1063916/full
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author Iva Arato
Stefano Giovagnoli
Alessandro Di Michele
Catia Bellucci
Cinzia Lilli
Maria Chiara Aglietti
Desirée Bartolini
Angela Gambelunghe
Giacomo Muzi
Mario Calvitti
Elena Eugeni
Francesco Gaggia
Tiziano Baroni
Francesca Mancuso
Giovanni Luca
Giovanni Luca
Giovanni Luca
author_facet Iva Arato
Stefano Giovagnoli
Alessandro Di Michele
Catia Bellucci
Cinzia Lilli
Maria Chiara Aglietti
Desirée Bartolini
Angela Gambelunghe
Giacomo Muzi
Mario Calvitti
Elena Eugeni
Francesco Gaggia
Tiziano Baroni
Francesca Mancuso
Giovanni Luca
Giovanni Luca
Giovanni Luca
author_sort Iva Arato
collection DOAJ
description Lately, nickel oxide nanoparticles (NiO NPs) have been employed in different industrial and biomedical fields. Several studies have reported that NiO NPs may affect the development of reproductive organs inducing oxidative stress and, resulting in male infertility. We investigated the in vitro effects of NiO NPs on porcine pre-pubertal Sertoli cells (SCs) which undergone acute (24 h) and chronic (from 1 up to 3 weeks) exposure at two subtoxic doses of NiO NPs of 1 μg/ml and 5 μg/ml. After NiO NPs exposure we performed the following analysis: (a) SCs morphological analysis (Light Microscopy); (b) ROS production and oxidative DNA damage, gene expression of antioxidant enzymes (c) SCs functionality (AMH, inhibin B Real-time PCR analysis and ELISA test); (d) apoptosis (WB analysis); (e) pro-inflammatory cytokines (Real-time PCR analysis), and (f) MAPK kinase signaling pathway (WB analysis). We found that the SCs exposed to both subtoxic doses of NiO NPs didn’t sustain substantial morphological changes. NiO NPs exposure, at each concentration, reported a marked increase of intracellular ROS at the third week of treatment and DNA damage at all exposure times. We demonstrated, un up-regulation of SOD and HO-1 gene expression, at both concentrations tested. The both subtoxic doses of NiO NPs detected a down-regulation of AMH and inhibin B gene expression and secreted proteins. Only the 5 μg/ml dose induced the activation of caspase-3 at the third week. At the two subtoxic doses of NiO NPs a clear pro-inflammatory response was resulted in an up-regulation of TNF-α and IL-6 in terms of mRNA. Finally, an increased phosphorylation ratio of p-ERK1/2, p-38 and p-AKT was observed up to the third week, at both concentrations. Our results show the negative impact of subtoxic doses NiO NPs chronic exposure on porcine SCs functionality and viability.
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spelling doaj-art-3c5256be4ff940bb97cd2a282a0335032025-08-20T03:21:46ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-03-011410.3389/fendo.2023.10639161063916Nickel oxide nanoparticles exposure as a risk factor for male infertility: “In vitro” effects on porcine pre-pubertal Sertoli cellsIva Arato0Stefano Giovagnoli1Alessandro Di Michele2Catia Bellucci3Cinzia Lilli4Maria Chiara Aglietti5Desirée Bartolini6Angela Gambelunghe7Giacomo Muzi8Mario Calvitti9Elena Eugeni10Francesco Gaggia11Tiziano Baroni12Francesca Mancuso13Giovanni Luca14Giovanni Luca15Giovanni Luca16Department of Medicine and Surgery, University of Perugia, Perugia, ItalyDepartment of Pharmaceutical Sciences, University of Perugia, Perugia, ItalyDepartment of Physics and Geology, University of Perugia, Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Perugia, ItalyInternal Medicine Endocrine and Metabolic Sciences Unit, Santa Maria della Misericordia Hospital of Perugia, Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Perugia, ItalyInternational Biotechnological Center for Endocrine, Metabolic and Embryo-Reproductive Translational Research (CIRTEMER), Department of Medicine and Surgery, University of Perugia, Perugia, ItalyDivision of Medical Andrology and Endocrinology of Reproduction, Saint Mary Hospital, Terni, ItalyLately, nickel oxide nanoparticles (NiO NPs) have been employed in different industrial and biomedical fields. Several studies have reported that NiO NPs may affect the development of reproductive organs inducing oxidative stress and, resulting in male infertility. We investigated the in vitro effects of NiO NPs on porcine pre-pubertal Sertoli cells (SCs) which undergone acute (24 h) and chronic (from 1 up to 3 weeks) exposure at two subtoxic doses of NiO NPs of 1 μg/ml and 5 μg/ml. After NiO NPs exposure we performed the following analysis: (a) SCs morphological analysis (Light Microscopy); (b) ROS production and oxidative DNA damage, gene expression of antioxidant enzymes (c) SCs functionality (AMH, inhibin B Real-time PCR analysis and ELISA test); (d) apoptosis (WB analysis); (e) pro-inflammatory cytokines (Real-time PCR analysis), and (f) MAPK kinase signaling pathway (WB analysis). We found that the SCs exposed to both subtoxic doses of NiO NPs didn’t sustain substantial morphological changes. NiO NPs exposure, at each concentration, reported a marked increase of intracellular ROS at the third week of treatment and DNA damage at all exposure times. We demonstrated, un up-regulation of SOD and HO-1 gene expression, at both concentrations tested. The both subtoxic doses of NiO NPs detected a down-regulation of AMH and inhibin B gene expression and secreted proteins. Only the 5 μg/ml dose induced the activation of caspase-3 at the third week. At the two subtoxic doses of NiO NPs a clear pro-inflammatory response was resulted in an up-regulation of TNF-α and IL-6 in terms of mRNA. Finally, an increased phosphorylation ratio of p-ERK1/2, p-38 and p-AKT was observed up to the third week, at both concentrations. Our results show the negative impact of subtoxic doses NiO NPs chronic exposure on porcine SCs functionality and viability.https://www.frontiersin.org/articles/10.3389/fendo.2023.1063916/fullSertoli cellsnickel oxide nanoparticlesROScometMAPK pathways
spellingShingle Iva Arato
Stefano Giovagnoli
Alessandro Di Michele
Catia Bellucci
Cinzia Lilli
Maria Chiara Aglietti
Desirée Bartolini
Angela Gambelunghe
Giacomo Muzi
Mario Calvitti
Elena Eugeni
Francesco Gaggia
Tiziano Baroni
Francesca Mancuso
Giovanni Luca
Giovanni Luca
Giovanni Luca
Nickel oxide nanoparticles exposure as a risk factor for male infertility: “In vitro” effects on porcine pre-pubertal Sertoli cells
Frontiers in Endocrinology
Sertoli cells
nickel oxide nanoparticles
ROS
comet
MAPK pathways
title Nickel oxide nanoparticles exposure as a risk factor for male infertility: “In vitro” effects on porcine pre-pubertal Sertoli cells
title_full Nickel oxide nanoparticles exposure as a risk factor for male infertility: “In vitro” effects on porcine pre-pubertal Sertoli cells
title_fullStr Nickel oxide nanoparticles exposure as a risk factor for male infertility: “In vitro” effects on porcine pre-pubertal Sertoli cells
title_full_unstemmed Nickel oxide nanoparticles exposure as a risk factor for male infertility: “In vitro” effects on porcine pre-pubertal Sertoli cells
title_short Nickel oxide nanoparticles exposure as a risk factor for male infertility: “In vitro” effects on porcine pre-pubertal Sertoli cells
title_sort nickel oxide nanoparticles exposure as a risk factor for male infertility in vitro effects on porcine pre pubertal sertoli cells
topic Sertoli cells
nickel oxide nanoparticles
ROS
comet
MAPK pathways
url https://www.frontiersin.org/articles/10.3389/fendo.2023.1063916/full
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