Molecular insight into reproductive toxicity and transgenerational effects of Cadmium exposure on Drosophila melanogaster
Cadmium (Cd), a widespread and serious environmental pollutant, has recently garnered increasing scientific scrutiny due to its profound adverse effects. Although the evidence for Cd-induced reproductive toxicity is well established, it remains elusive on the intricate dose-response relationship and...
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Elsevier
2025-02-01
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author | Yi Pan Ke Fan Linhao Zong Yantao Luo Xin Ni Dong Chen Jinjun Qian Fei Ma Jie Cheng Miao Guan |
author_facet | Yi Pan Ke Fan Linhao Zong Yantao Luo Xin Ni Dong Chen Jinjun Qian Fei Ma Jie Cheng Miao Guan |
author_sort | Yi Pan |
collection | DOAJ |
description | Cadmium (Cd), a widespread and serious environmental pollutant, has recently garnered increasing scientific scrutiny due to its profound adverse effects. Although the evidence for Cd-induced reproductive toxicity is well established, it remains elusive on the intricate dose-response relationship and underlying molecular mechanisms, especially for transgenerational toxicity in animals. Here, we employed fruit fly (Drosophila melanogaster) as a model organism to examine the reproductive performance across five generations by parental exposure to varying concentrations of Cd (5, 50, and 500 μM). Firstly, our observations on the number of eggs laid, pupae formed, and adult flies emerged on the directly exposed generation (F0) confirmed a dose-dependent decline in fecundity. Transcriptome analysis revealed that, Cd-induced oxidative stress and ion transport disruption in the F0 generation could underlie synaptic dysfunction and impaired follicle cell development, impacting reproductive behavior and oocyte fertility. Employing dose-response analysis, Wnt signaling pathway and mTOR signaling pathway were identified as early molecular responses to Cd-induced toxicity. Secondly, sustained detrimental effects were observed for at least two to three generations after Cd removal. At the epigenetic level, Cd could perturb fecundity across generations by modulating Dnmt2 expression, a pivotal regulator of methylation processes. Moreover, despite phenotypic recovery in F4, persistent molecular changes indicate enduring toxicity, highlighting the need for vigilance against environmental Cd contamination and its long-term effects. Collectively, our findings enhance the understanding of Cd-induced reproductive toxicity and its transgenerational effects, and highlight the need to further improve the assessment of the multigenerational consequences of environmental Cd contamination. |
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institution | Kabale University |
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language | English |
publishDate | 2025-02-01 |
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spelling | doaj-art-7e4f2419ad624e9fb0bcbb527907e4f92025-02-10T04:33:29ZengElsevierEcotoxicology and Environmental Safety0147-65132025-02-01291117870Molecular insight into reproductive toxicity and transgenerational effects of Cadmium exposure on Drosophila melanogasterYi Pan0Ke Fan1Linhao Zong2Yantao Luo3Xin Ni4Dong Chen5Jinjun Qian6Fei Ma7Jie Cheng8Miao Guan9Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Rd, Nanjing, Jiangsu 210023, ChinaJiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Rd, Nanjing, Jiangsu 210023, ChinaJiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Rd, Nanjing, Jiangsu 210023, ChinaJiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Rd, Nanjing, Jiangsu 210023, ChinaJiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Rd, Nanjing, Jiangsu 210023, ChinaSchool of Resources and Environmental Engineering, Jiangsu University of Technology, 1801 Zhongwu, Changzhou, Jiangsu 213001, ChinaSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine., 138 Xianlin Ave, Nanjing, Jiangsu 210023, ChinaJiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Rd, Nanjing, Jiangsu 210023, ChinaCenter for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China; Corresponding author at: Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China.Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Rd, Nanjing, Jiangsu 210023, China; Correspondence to: College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu 210023, China.Cadmium (Cd), a widespread and serious environmental pollutant, has recently garnered increasing scientific scrutiny due to its profound adverse effects. Although the evidence for Cd-induced reproductive toxicity is well established, it remains elusive on the intricate dose-response relationship and underlying molecular mechanisms, especially for transgenerational toxicity in animals. Here, we employed fruit fly (Drosophila melanogaster) as a model organism to examine the reproductive performance across five generations by parental exposure to varying concentrations of Cd (5, 50, and 500 μM). Firstly, our observations on the number of eggs laid, pupae formed, and adult flies emerged on the directly exposed generation (F0) confirmed a dose-dependent decline in fecundity. Transcriptome analysis revealed that, Cd-induced oxidative stress and ion transport disruption in the F0 generation could underlie synaptic dysfunction and impaired follicle cell development, impacting reproductive behavior and oocyte fertility. Employing dose-response analysis, Wnt signaling pathway and mTOR signaling pathway were identified as early molecular responses to Cd-induced toxicity. Secondly, sustained detrimental effects were observed for at least two to three generations after Cd removal. At the epigenetic level, Cd could perturb fecundity across generations by modulating Dnmt2 expression, a pivotal regulator of methylation processes. Moreover, despite phenotypic recovery in F4, persistent molecular changes indicate enduring toxicity, highlighting the need for vigilance against environmental Cd contamination and its long-term effects. Collectively, our findings enhance the understanding of Cd-induced reproductive toxicity and its transgenerational effects, and highlight the need to further improve the assessment of the multigenerational consequences of environmental Cd contamination.http://www.sciencedirect.com/science/article/pii/S0147651325002064CadmiumReproductive toxicityBenchmark dose methodologyTransgenerational effectEpigenetic modificationsDrosophila melanogaster |
spellingShingle | Yi Pan Ke Fan Linhao Zong Yantao Luo Xin Ni Dong Chen Jinjun Qian Fei Ma Jie Cheng Miao Guan Molecular insight into reproductive toxicity and transgenerational effects of Cadmium exposure on Drosophila melanogaster Ecotoxicology and Environmental Safety Cadmium Reproductive toxicity Benchmark dose methodology Transgenerational effect Epigenetic modifications Drosophila melanogaster |
title | Molecular insight into reproductive toxicity and transgenerational effects of Cadmium exposure on Drosophila melanogaster |
title_full | Molecular insight into reproductive toxicity and transgenerational effects of Cadmium exposure on Drosophila melanogaster |
title_fullStr | Molecular insight into reproductive toxicity and transgenerational effects of Cadmium exposure on Drosophila melanogaster |
title_full_unstemmed | Molecular insight into reproductive toxicity and transgenerational effects of Cadmium exposure on Drosophila melanogaster |
title_short | Molecular insight into reproductive toxicity and transgenerational effects of Cadmium exposure on Drosophila melanogaster |
title_sort | molecular insight into reproductive toxicity and transgenerational effects of cadmium exposure on drosophila melanogaster |
topic | Cadmium Reproductive toxicity Benchmark dose methodology Transgenerational effect Epigenetic modifications Drosophila melanogaster |
url | http://www.sciencedirect.com/science/article/pii/S0147651325002064 |
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