Exposure to Sucralose and Its Effects on Testicular Damage and Male Infertility: Insights into Oxidative Stress and Autophagy.

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Title: Exposure to Sucralose and Its Effects on Testicular Damage and Male Infertility: Insights into Oxidative Stress and Autophagy.
Authors: Yi-Fen Chiang1, Yang-Ching Chen1,2,3,4, Ko-Chieh Huang1, Ali, Mohamed5,6, Shih-Min Hsia1,7,8 bryanhsia@tmu.edu.tw
Source: Environmental Health Perspectives. Jun2026, Vol. 134 Issue 2, p170-183. 14p.
Subject Terms: *Animal experimentation, Spermatozoa physiology, Risk assessment, Biological models, In vitro studies, Testosterone, Dietary sucrose, Autophagy, Reproductive health, Hormones, Research funding, Data analysis, T-test (Statistics), Statistical hypothesis testing, Infertility, Two-way analysis of variance, Kruskal-Wallis Test, Enzyme-linked immunosorbent assay, Oxidative stress, Cellular signal transduction, In vivo studies, Descriptive statistics, Mann Whitney U Test, Mice, Cell lines, Cell culture, Lipid peroxidation (Biology), Testicular diseases, Men's health, Testis, Western immunoblotting, Statistics, One-way analysis of variance, Sperm motility, Cell survival, Stains & staining (Microscopy), Data analysis software, Comparative studies, Cell receptors, Disease risk factors
Abstract: BACKGROUND: The impact of non-nutritive sweeteners on male reproductive health, particularly at the cellular level, remains insufficiently explored. Sucralose’s high stability and resistance to degradation during wastewater treatment raises concerns about its long-term environmental and health impacts. Whether sucralose consumption correlates with reduced reproductive hormone levels and testicular damage remains unclear, and the underlying mechanisms require further investigation. OBJECTIVES: This study aims to investigate the influence of sucralose on cell damage and reproductive health in males. METHODS: The male mouse Leydig cell line TM3 and Sertoli cell line TM4 were used to evaluate sucralose-associated cellular damage. In vitro experiments assessed cell survival rates and the potential disruption of autophagy. Additionally, male SD rats were exposed to sucralose via oral gavage for two months at doses reflecting the acceptable daily intake (ADI) to evaluate sperm viability and reproductive health. RESULTS: In vitro experiments demonstrated that cells exposed to sucralose had significantly lower survival rates. Sucralose exposure significantly reduced cell viability in TM3 and TM4 cells, induced oxidative stress, and disrupted autophagic flux by impairing autophagosome-lysosome fusion. Additionally, sucralose downregulated T1R3 protein expression, suggesting a role for sweet taste receptor signaling in testicular cell regulation. In vivo, chronic oral exposure to sucralose led to decreased sperm viability and impaired reproductive function, including altered testicular morphology and suppressed steroidogenesis. DISCUSSION: These findings provide new insights into the adverse effects of sucralose on male reproductive physiology, highlighting its role in disrupting autophagy, inducing oxidative stress, and impairing reproductive function. The environmental persistence of sucralose and its potential leakage into wastewater systems present broader implications for public health and ecological stability. This study underscores the importance of carefully evaluating non-nutritive sweeteners in the diet and calls for stricter food safety regulations and wastewater management practices to mitigate potential risks. [ABSTRACT FROM AUTHOR]
Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Label: Title
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  Data: Exposure to Sucralose and Its Effects on Testicular Damage and Male Infertility: Insights into Oxidative Stress and Autophagy.
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  Data: <searchLink fieldCode="AR" term="%22Yi-Fen+Chiang%22">Yi-Fen Chiang</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Yang-Ching+Chen%22">Yang-Ching Chen</searchLink><relatesTo>1,2,3,4</relatesTo><br /><searchLink fieldCode="AR" term="%22Ko-Chieh+Huang%22">Ko-Chieh Huang</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Ali%2C+Mohamed%22">Ali, Mohamed</searchLink><relatesTo>5,6</relatesTo><br /><searchLink fieldCode="AR" term="%22Shih-Min+Hsia%22">Shih-Min Hsia</searchLink><relatesTo>1,7,8</relatesTo><i> bryanhsia@tmu.edu.tw</i>
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  Data: <searchLink fieldCode="JN" term="%22Environmental+Health+Perspectives%22">Environmental Health Perspectives</searchLink>. Jun2026, Vol. 134 Issue 2, p170-183. 14p.
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  Data: *<searchLink fieldCode="DE" term="%22Animal+experimentation%22">Animal experimentation</searchLink><br /><searchLink fieldCode="DE" term="%22Spermatozoa+physiology%22">Spermatozoa physiology</searchLink><br /><searchLink fieldCode="DE" term="%22Risk+assessment%22">Risk assessment</searchLink><br /><searchLink fieldCode="DE" term="%22Biological+models%22">Biological models</searchLink><br /><searchLink fieldCode="DE" term="%22In+vitro+studies%22">In vitro studies</searchLink><br /><searchLink fieldCode="DE" term="%22Testosterone%22">Testosterone</searchLink><br /><searchLink fieldCode="DE" term="%22Dietary+sucrose%22">Dietary sucrose</searchLink><br /><searchLink fieldCode="DE" term="%22Autophagy%22">Autophagy</searchLink><br /><searchLink fieldCode="DE" term="%22Reproductive+health%22">Reproductive health</searchLink><br /><searchLink fieldCode="DE" term="%22Hormones%22">Hormones</searchLink><br /><searchLink fieldCode="DE" term="%22Research+funding%22">Research funding</searchLink><br /><searchLink fieldCode="DE" term="%22Data+analysis%22">Data analysis</searchLink><br /><searchLink fieldCode="DE" term="%22T-test+%28Statistics%29%22">T-test (Statistics)</searchLink><br /><searchLink fieldCode="DE" term="%22Statistical+hypothesis+testing%22">Statistical hypothesis testing</searchLink><br /><searchLink fieldCode="DE" term="%22Infertility%22">Infertility</searchLink><br /><searchLink fieldCode="DE" term="%22Two-way+analysis+of+variance%22">Two-way analysis of variance</searchLink><br /><searchLink fieldCode="DE" term="%22Kruskal-Wallis+Test%22">Kruskal-Wallis Test</searchLink><br /><searchLink fieldCode="DE" term="%22Enzyme-linked+immunosorbent+assay%22">Enzyme-linked immunosorbent assay</searchLink><br /><searchLink fieldCode="DE" term="%22Oxidative+stress%22">Oxidative stress</searchLink><br /><searchLink fieldCode="DE" term="%22Cellular+signal+transduction%22">Cellular signal transduction</searchLink><br /><searchLink fieldCode="DE" term="%22In+vivo+studies%22">In vivo studies</searchLink><br /><searchLink fieldCode="DE" term="%22Descriptive+statistics%22">Descriptive statistics</searchLink><br /><searchLink fieldCode="DE" term="%22Mann+Whitney+U+Test%22">Mann Whitney U Test</searchLink><br /><searchLink fieldCode="DE" term="%22Mice%22">Mice</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+lines%22">Cell lines</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+culture%22">Cell culture</searchLink><br /><searchLink fieldCode="DE" term="%22Lipid+peroxidation+%28Biology%29%22">Lipid peroxidation (Biology)</searchLink><br /><searchLink fieldCode="DE" term="%22Testicular+diseases%22">Testicular diseases</searchLink><br /><searchLink fieldCode="DE" term="%22Men's+health%22">Men's health</searchLink><br /><searchLink fieldCode="DE" term="%22Testis%22">Testis</searchLink><br /><searchLink fieldCode="DE" term="%22Western+immunoblotting%22">Western immunoblotting</searchLink><br /><searchLink fieldCode="DE" term="%22Statistics%22">Statistics</searchLink><br /><searchLink fieldCode="DE" term="%22One-way+analysis+of+variance%22">One-way analysis of variance</searchLink><br /><searchLink fieldCode="DE" term="%22Sperm+motility%22">Sperm motility</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+survival%22">Cell survival</searchLink><br /><searchLink fieldCode="DE" term="%22Stains+%26+staining+%28Microscopy%29%22">Stains & staining (Microscopy)</searchLink><br /><searchLink fieldCode="DE" term="%22Data+analysis+software%22">Data analysis software</searchLink><br /><searchLink fieldCode="DE" term="%22Comparative+studies%22">Comparative studies</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+receptors%22">Cell receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Disease+risk+factors%22">Disease risk factors</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: BACKGROUND: The impact of non-nutritive sweeteners on male reproductive health, particularly at the cellular level, remains insufficiently explored. Sucralose’s high stability and resistance to degradation during wastewater treatment raises concerns about its long-term environmental and health impacts. Whether sucralose consumption correlates with reduced reproductive hormone levels and testicular damage remains unclear, and the underlying mechanisms require further investigation. OBJECTIVES: This study aims to investigate the influence of sucralose on cell damage and reproductive health in males. METHODS: The male mouse Leydig cell line TM3 and Sertoli cell line TM4 were used to evaluate sucralose-associated cellular damage. In vitro experiments assessed cell survival rates and the potential disruption of autophagy. Additionally, male SD rats were exposed to sucralose via oral gavage for two months at doses reflecting the acceptable daily intake (ADI) to evaluate sperm viability and reproductive health. RESULTS: In vitro experiments demonstrated that cells exposed to sucralose had significantly lower survival rates. Sucralose exposure significantly reduced cell viability in TM3 and TM4 cells, induced oxidative stress, and disrupted autophagic flux by impairing autophagosome-lysosome fusion. Additionally, sucralose downregulated T1R3 protein expression, suggesting a role for sweet taste receptor signaling in testicular cell regulation. In vivo, chronic oral exposure to sucralose led to decreased sperm viability and impaired reproductive function, including altered testicular morphology and suppressed steroidogenesis. DISCUSSION: These findings provide new insights into the adverse effects of sucralose on male reproductive physiology, highlighting its role in disrupting autophagy, inducing oxidative stress, and impairing reproductive function. The environmental persistence of sucralose and its potential leakage into wastewater systems present broader implications for public health and ecological stability. This study underscores the importance of carefully evaluating non-nutritive sweeteners in the diet and calls for stricter food safety regulations and wastewater management practices to mitigate potential risks. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
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  Data: <i>Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1021/EHP.6c00314
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        Text: English
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        Type: general
      – SubjectFull: Spermatozoa physiology
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      – SubjectFull: Risk assessment
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      – SubjectFull: Testosterone
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      – SubjectFull: Dietary sucrose
        Type: general
      – SubjectFull: Autophagy
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      – SubjectFull: Reproductive health
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      – SubjectFull: Two-way analysis of variance
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      – SubjectFull: In vivo studies
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      – SubjectFull: Descriptive statistics
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        Type: general
      – SubjectFull: Mice
        Type: general
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      – SubjectFull: Lipid peroxidation (Biology)
        Type: general
      – SubjectFull: Testicular diseases
        Type: general
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      – SubjectFull: One-way analysis of variance
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      – SubjectFull: Sperm motility
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      – SubjectFull: Cell receptors
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      – SubjectFull: Disease risk factors
        Type: general
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      – TitleFull: Exposure to Sucralose and Its Effects on Testicular Damage and Male Infertility: Insights into Oxidative Stress and Autophagy.
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              M: 06
              Text: Jun2026
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              Y: 2026
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