Analysis of toxicity and mechanisms of busulfan in non-obstructive azoospermia: A genomic and toxicological approach integrating molecular docking, single-cell sequencing, and experimentation in vivo
Environmental pollutants, including chemical contaminants, heavy metals, and pesticides, have been linked to adverse effects on male reproductive health, particularly sperm quality. Non-obstructive azoospermia (NOA) is a severe form of male infertility caused by intrinsic testicular dysfunction, lea...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325002143 |
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| author | Yanggang Hong Qichao Yuan Yi Wang Deqi Wang Xiaoju Guan Congde Chen |
| author_facet | Yanggang Hong Qichao Yuan Yi Wang Deqi Wang Xiaoju Guan Congde Chen |
| author_sort | Yanggang Hong |
| collection | DOAJ |
| description | Environmental pollutants, including chemical contaminants, heavy metals, and pesticides, have been linked to adverse effects on male reproductive health, particularly sperm quality. Non-obstructive azoospermia (NOA) is a severe form of male infertility caused by intrinsic testicular dysfunction, leading to a complete absence of sperm in the ejaculate. Busulfan, an alkylating chemotherapeutic agent widely used to treat chronic myelogenous leukemia, is known to induce NOA through its toxic effects on spermatogonial stem cells (SSCs). This study aimed to identify key molecular targets and pathways disrupted by busulfan in the testicular environment. By integrating molecular docking, single-cell RNA sequencing, and in vivo experimentation, the study identified POLE and LRAT as critical proteins. These proteins were shown to interact strongly with busulfan, leading to genomic instability and increased germ cell apoptosis during spermatogenesis. Additionally, the immune landscape of NOA-affected testes revealed significant changes in immune cell infiltration, potentially worsening the condition. These findings offer new insights into the mechanisms of busulfan-induced NOA and suggest potential therapeutic targets for preserving male fertility in chemotherapy patients. This research advances the understanding of chemotherapy-induced reproductive toxicity and emphasizes the need for strategies to reduce its negative effects on fertility. |
| format | Article |
| id | doaj-art-6e7b4012f0504290a771abd06a981f9a |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-6e7b4012f0504290a771abd06a981f9a2025-02-12T05:30:23ZengElsevierEcotoxicology and Environmental Safety0147-65132025-02-01291117878Analysis of toxicity and mechanisms of busulfan in non-obstructive azoospermia: A genomic and toxicological approach integrating molecular docking, single-cell sequencing, and experimentation in vivoYanggang Hong0Qichao Yuan1Yi Wang2Deqi Wang3Xiaoju Guan4Congde Chen5Department of pediatric urology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Children Genitourinary Diseases of Wenzhou, Wenzhou, Zhejiang 325027, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaDepartment of pediatric urology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Children Genitourinary Diseases of Wenzhou, Wenzhou, Zhejiang 325027, ChinaThe First School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaThe First School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaDepartment of pediatric urology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Children Genitourinary Diseases of Wenzhou, Wenzhou, Zhejiang 325027, China; Corresponding authors at: Department of pediatric urology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.Department of pediatric urology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Children Genitourinary Diseases of Wenzhou, Wenzhou, Zhejiang 325027, China; Corresponding authors at: Department of pediatric urology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.Environmental pollutants, including chemical contaminants, heavy metals, and pesticides, have been linked to adverse effects on male reproductive health, particularly sperm quality. Non-obstructive azoospermia (NOA) is a severe form of male infertility caused by intrinsic testicular dysfunction, leading to a complete absence of sperm in the ejaculate. Busulfan, an alkylating chemotherapeutic agent widely used to treat chronic myelogenous leukemia, is known to induce NOA through its toxic effects on spermatogonial stem cells (SSCs). This study aimed to identify key molecular targets and pathways disrupted by busulfan in the testicular environment. By integrating molecular docking, single-cell RNA sequencing, and in vivo experimentation, the study identified POLE and LRAT as critical proteins. These proteins were shown to interact strongly with busulfan, leading to genomic instability and increased germ cell apoptosis during spermatogenesis. Additionally, the immune landscape of NOA-affected testes revealed significant changes in immune cell infiltration, potentially worsening the condition. These findings offer new insights into the mechanisms of busulfan-induced NOA and suggest potential therapeutic targets for preserving male fertility in chemotherapy patients. This research advances the understanding of chemotherapy-induced reproductive toxicity and emphasizes the need for strategies to reduce its negative effects on fertility.http://www.sciencedirect.com/science/article/pii/S0147651325002143Non-obstructive azoospermiaBusulfanToxicologyMale reproductionMolecular docking |
| spellingShingle | Yanggang Hong Qichao Yuan Yi Wang Deqi Wang Xiaoju Guan Congde Chen Analysis of toxicity and mechanisms of busulfan in non-obstructive azoospermia: A genomic and toxicological approach integrating molecular docking, single-cell sequencing, and experimentation in vivo Ecotoxicology and Environmental Safety Non-obstructive azoospermia Busulfan Toxicology Male reproduction Molecular docking |
| title | Analysis of toxicity and mechanisms of busulfan in non-obstructive azoospermia: A genomic and toxicological approach integrating molecular docking, single-cell sequencing, and experimentation in vivo |
| title_full | Analysis of toxicity and mechanisms of busulfan in non-obstructive azoospermia: A genomic and toxicological approach integrating molecular docking, single-cell sequencing, and experimentation in vivo |
| title_fullStr | Analysis of toxicity and mechanisms of busulfan in non-obstructive azoospermia: A genomic and toxicological approach integrating molecular docking, single-cell sequencing, and experimentation in vivo |
| title_full_unstemmed | Analysis of toxicity and mechanisms of busulfan in non-obstructive azoospermia: A genomic and toxicological approach integrating molecular docking, single-cell sequencing, and experimentation in vivo |
| title_short | Analysis of toxicity and mechanisms of busulfan in non-obstructive azoospermia: A genomic and toxicological approach integrating molecular docking, single-cell sequencing, and experimentation in vivo |
| title_sort | analysis of toxicity and mechanisms of busulfan in non obstructive azoospermia a genomic and toxicological approach integrating molecular docking single cell sequencing and experimentation in vivo |
| topic | Non-obstructive azoospermia Busulfan Toxicology Male reproduction Molecular docking |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325002143 |
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