The consequences of tetraploidy on Caenorhabditis elegans physiology and sensitivity to chemotherapeutics
Abstract Polyploid cells contain more than two copies of each chromosome. Polyploidy has important roles in development, evolution, and tissue regeneration/repair, and can arise as a programmed polyploidization event or be triggered by stress. Cancer cells are often polyploid. C. elegans nematodes a...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-45225-w |
| _version_ | 1797452912943693824 |
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| author | Kelly R. Misare Elizabeth A. Ampolini Hyland C. Gonzalez Kaitlan A. Sullivan Xin Li Camille Miller Bintou Sosseh Jaclyn B. Dunne Christina Voelkel-Johnson Kacy L. Gordon Jessica H. Hartman |
| author_facet | Kelly R. Misare Elizabeth A. Ampolini Hyland C. Gonzalez Kaitlan A. Sullivan Xin Li Camille Miller Bintou Sosseh Jaclyn B. Dunne Christina Voelkel-Johnson Kacy L. Gordon Jessica H. Hartman |
| author_sort | Kelly R. Misare |
| collection | DOAJ |
| description | Abstract Polyploid cells contain more than two copies of each chromosome. Polyploidy has important roles in development, evolution, and tissue regeneration/repair, and can arise as a programmed polyploidization event or be triggered by stress. Cancer cells are often polyploid. C. elegans nematodes are typically diploid, but stressors such as heat shock and starvation can trigger the production of tetraploid offspring. In this study, we utilized a recently published protocol to generate stable tetraploid strains of C. elegans and compared their physiological traits and sensitivity to two DNA-damaging chemotherapeutic drugs, cisplatin and doxorubicin. As prior studies have shown, tetraploid worms are approximately 30% longer, shorter-lived, and have a smaller brood size than diploids. We investigated the reproductive defect further, determining that tetraploid worms have a shorter overall germline length, a higher rate of germ cell apoptosis, more aneuploidy in oocytes and offspring, and larger oocytes and embryos. We also found that tetraploid worms are modestly protected from growth delay from the chemotherapeutics but are similarly or more sensitive to reproductive toxicity. Transcriptomic analysis revealed differentially expressed pathways that may contribute to sensitivity to stress. This study reveals phenotypic consequences of whole-animal tetraploidy that make C. elegans an excellent model for ploidy differences. |
| first_indexed | 2024-03-09T15:15:32Z |
| format | Article |
| id | doaj.art-5a58c60f1ad04f77b4fbd7f303a7d381 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:15:32Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5a58c60f1ad04f77b4fbd7f303a7d3812023-11-26T13:06:23ZengNature PortfolioScientific Reports2045-23222023-10-0113111610.1038/s41598-023-45225-wThe consequences of tetraploidy on Caenorhabditis elegans physiology and sensitivity to chemotherapeuticsKelly R. Misare0Elizabeth A. Ampolini1Hyland C. Gonzalez2Kaitlan A. Sullivan3Xin Li4Camille Miller5Bintou Sosseh6Jaclyn B. Dunne7Christina Voelkel-Johnson8Kacy L. Gordon9Jessica H. Hartman10Department of Biochemistry and Molecular Biology, College of Medicine, Medical University of South CarolinaDepartment of Biochemistry and Molecular Biology, College of Medicine, Medical University of South CarolinaDepartment of Biochemistry and Molecular Biology, College of Medicine, Medical University of South CarolinaDepartment of Biochemistry and Molecular Biology, College of Medicine, Medical University of South CarolinaDepartment of Biology, College of Arts and Sciences, University of North CarolinaDepartment of Biology, College of Arts and Sciences, University of North CarolinaDepartment of Biology, College of Arts and Sciences, University of North CarolinaDepartment of Biochemistry and Molecular Biology, College of Medicine, Medical University of South CarolinaDepartment of Microbiology and Immunology, College of Medicine, Medical University of South CarolinaDepartment of Biology, College of Arts and Sciences, University of North CarolinaDepartment of Biochemistry and Molecular Biology, College of Medicine, Medical University of South CarolinaAbstract Polyploid cells contain more than two copies of each chromosome. Polyploidy has important roles in development, evolution, and tissue regeneration/repair, and can arise as a programmed polyploidization event or be triggered by stress. Cancer cells are often polyploid. C. elegans nematodes are typically diploid, but stressors such as heat shock and starvation can trigger the production of tetraploid offspring. In this study, we utilized a recently published protocol to generate stable tetraploid strains of C. elegans and compared their physiological traits and sensitivity to two DNA-damaging chemotherapeutic drugs, cisplatin and doxorubicin. As prior studies have shown, tetraploid worms are approximately 30% longer, shorter-lived, and have a smaller brood size than diploids. We investigated the reproductive defect further, determining that tetraploid worms have a shorter overall germline length, a higher rate of germ cell apoptosis, more aneuploidy in oocytes and offspring, and larger oocytes and embryos. We also found that tetraploid worms are modestly protected from growth delay from the chemotherapeutics but are similarly or more sensitive to reproductive toxicity. Transcriptomic analysis revealed differentially expressed pathways that may contribute to sensitivity to stress. This study reveals phenotypic consequences of whole-animal tetraploidy that make C. elegans an excellent model for ploidy differences.https://doi.org/10.1038/s41598-023-45225-w |
| spellingShingle | Kelly R. Misare Elizabeth A. Ampolini Hyland C. Gonzalez Kaitlan A. Sullivan Xin Li Camille Miller Bintou Sosseh Jaclyn B. Dunne Christina Voelkel-Johnson Kacy L. Gordon Jessica H. Hartman The consequences of tetraploidy on Caenorhabditis elegans physiology and sensitivity to chemotherapeutics Scientific Reports |
| title | The consequences of tetraploidy on Caenorhabditis elegans physiology and sensitivity to chemotherapeutics |
| title_full | The consequences of tetraploidy on Caenorhabditis elegans physiology and sensitivity to chemotherapeutics |
| title_fullStr | The consequences of tetraploidy on Caenorhabditis elegans physiology and sensitivity to chemotherapeutics |
| title_full_unstemmed | The consequences of tetraploidy on Caenorhabditis elegans physiology and sensitivity to chemotherapeutics |
| title_short | The consequences of tetraploidy on Caenorhabditis elegans physiology and sensitivity to chemotherapeutics |
| title_sort | consequences of tetraploidy on caenorhabditis elegans physiology and sensitivity to chemotherapeutics |
| url | https://doi.org/10.1038/s41598-023-45225-w |
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