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<p>This study investigated the dose-dependent effects of intratesticular zinc oxide nanoparticles (ZnO NPs) on reproductive toxicity in male Wistar rats, evaluating their potential as a chemical castration agent. Fifty rats, weighing 250–300&#xa0;g and aged 12–14 weeks, were divided into five groups: control, sham (normal saline), and ZnO NPs at 5&#xa0;mg/mL, 10&#xa0;mg/mL, and 25&#xa0;mg/mL. ZnO NPs (&lt; 100&#xa0;nm) were dissolved in saline and injected into the caudal testis. After 60 days, assessments included testicular oxidative stress markers (total antioxidant capacity [TAC], catalase [CAT], glutathione peroxidase [GPx], superoxide dismutase [SOD], malondialdehyde [MDA], nitric oxide [NO]), epididymal sperm parameters (count, motility, viability, morphology, DNA integrity, plasma membrane functionality), histopathological and morphometric evaluations (Johnsen/Cosentino scores, seminiferous tubule diameter [STsD], Sertoli cell index [SCI], repopulation index [RI], meiotic index [MI], Leydig cell nuclear diameter [LCND], tubular differentiation index [TDI], spermiogenesis index [SPI]), apoptosis-related gene expression (<i>Caspase-3</i>, <i>Caspase-8</i>, <i>Caspase-9</i>, <i>Fas</i>, <i>Bcl-2</i> via quantitative real-time polymerase chain reaction [qRT-PCR]), and fertility indices post-mating. Results revealed dose-dependent impairments: reduced sperm concentration, motility, viability, and membrane integrity; increased DNA damage and morphological abnormalities; depleted antioxidants with elevated MDA/NO; severe histopathological changes including tubule atrophy and cell loss; upregulation of pro-apoptotic genes and downregulation of <i>Bcl-2</i>; and reduced fertility with higher implantation losses. While ZnO NPs exhibit beneficial effects, such as antioxidant and antimicrobial properties at low concentrations (typically &lt; 5&#xa0;mg/mL or 1–50&#xa0;mg/kg in oral/intraperitoneal studies), they become toxic at higher doses (≥ 10&#xa0;mg/mL in this intratesticular model), primarily through oxidative stress and apoptosis. These findings, despite species-specific and route-dependent variations, underscore ZnO NPs’ detrimental impact on spermatogenesis, emphasizing the need for cautious application to mitigate risks to male fertility.</p>

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Efficacy of zinc oxide nanoparticles in chemical castration of male Wistar rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月29日

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  • Mehdi Kian,
  • Ali Soleimanzadeh,
  • Shahram Javadi,
  • Gholamreza Najafi

摘要

This study investigated the dose-dependent effects of intratesticular zinc oxide nanoparticles (ZnO NPs) on reproductive toxicity in male Wistar rats, evaluating their potential as a chemical castration agent. Fifty rats, weighing 250–300 g and aged 12–14 weeks, were divided into five groups: control, sham (normal saline), and ZnO NPs at 5 mg/mL, 10 mg/mL, and 25 mg/mL. ZnO NPs (< 100 nm) were dissolved in saline and injected into the caudal testis. After 60 days, assessments included testicular oxidative stress markers (total antioxidant capacity [TAC], catalase [CAT], glutathione peroxidase [GPx], superoxide dismutase [SOD], malondialdehyde [MDA], nitric oxide [NO]), epididymal sperm parameters (count, motility, viability, morphology, DNA integrity, plasma membrane functionality), histopathological and morphometric evaluations (Johnsen/Cosentino scores, seminiferous tubule diameter [STsD], Sertoli cell index [SCI], repopulation index [RI], meiotic index [MI], Leydig cell nuclear diameter [LCND], tubular differentiation index [TDI], spermiogenesis index [SPI]), apoptosis-related gene expression (Caspase-3, Caspase-8, Caspase-9, Fas, Bcl-2 via quantitative real-time polymerase chain reaction [qRT-PCR]), and fertility indices post-mating. Results revealed dose-dependent impairments: reduced sperm concentration, motility, viability, and membrane integrity; increased DNA damage and morphological abnormalities; depleted antioxidants with elevated MDA/NO; severe histopathological changes including tubule atrophy and cell loss; upregulation of pro-apoptotic genes and downregulation of Bcl-2; and reduced fertility with higher implantation losses. While ZnO NPs exhibit beneficial effects, such as antioxidant and antimicrobial properties at low concentrations (typically < 5 mg/mL or 1–50 mg/kg in oral/intraperitoneal studies), they become toxic at higher doses (≥ 10 mg/mL in this intratesticular model), primarily through oxidative stress and apoptosis. These findings, despite species-specific and route-dependent variations, underscore ZnO NPs’ detrimental impact on spermatogenesis, emphasizing the need for cautious application to mitigate risks to male fertility.