Tolerance to paternal genotoxic damage promotes survival during embryo development in zebrafish (Danio rerio)
Spermatozoa carry DNA damage that must be repaired by the oocyte machinery upon fertilization. Different strategies could be adopted by different vertebrates to face the paternal genotoxic damage. Mammals have strong sperm selection mechanisms and activate a zygotic DNA damage response (DDR) (includ...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2018-05-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/7/5/bio030130 |
| _version_ | 1818458525898113024 |
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| author | Cristina Fernández-Díez Silvia González-Rojo Marta Lombó M. Paz Herráez |
| author_facet | Cristina Fernández-Díez Silvia González-Rojo Marta Lombó M. Paz Herráez |
| author_sort | Cristina Fernández-Díez |
| collection | DOAJ |
| description | Spermatozoa carry DNA damage that must be repaired by the oocyte machinery upon fertilization. Different strategies could be adopted by different vertebrates to face the paternal genotoxic damage. Mammals have strong sperm selection mechanisms and activate a zygotic DNA damage response (DDR) (including cell cycle arrest, DNA repair and alternative apoptosis) in order to guarantee the genomic conformity of the reduced progeny. However, external fertilizers, with different reproductive strategies, seem to proceed distinctively. Previous results from our group showed a downregulation of apoptotic activity in trout embryos with a defective DNA repairing ability, suggesting that mechanisms of tolerance to damaged DNA could be activated in fish to maintain cell survival and to progress with development. In this work, zebrafish embryos were obtained from control or UV-irradiated sperm (carrying more than 10% of fragmented DNA but still preserving fertilization ability). DNA repair (γH2AX and 53BP1 foci), apoptotic activity, expression of genes related to DDR and malformation rates were analyzed throughout development. Results showed in the progeny from damaged sperm, an enhanced repairing activity at the mid-blastula transition stage that returned to its basal level at later stages, rendering at hatching a very high rate of multimalformed larvae. The study of transcriptional and post-translational activity of tp53 (ZDF-GENE-990415-270) revealed the activation of an intense DDR in those progenies. However, the downstream pro-apoptotic factor noxa (ZDF-GENE-070119-3) showed a significant downregulation, whereas the anti-apoptotic gene bcl2 (ZDF-GENE-051015-1) was upregulated, triggering a repressive apoptotic scenario in spite of a clear genomic instability. This repression can be explained by the observed upregulation of p53 isoform Δ113p53, which is known to enhance bcl2 transcription. Our results showed that tp53 is involved in DNA damage tolerance (DDT) pathways, allowing the embryo survival regardless of the paternal DNA damage. DDT could be an evolutionary mechanism in fish: tolerance to unrepaired sperm DNA could introduce new mutations, some of them potentially advantageous to face a changing environment. |
| first_indexed | 2024-12-14T22:59:51Z |
| format | Article |
| id | doaj.art-0cffd3ff6cda47bf9afdef90b7eeae2e |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-14T22:59:51Z |
| publishDate | 2018-05-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-0cffd3ff6cda47bf9afdef90b7eeae2e2022-12-21T22:44:29ZengThe Company of BiologistsBiology Open2046-63902018-05-017510.1242/bio.030130030130Tolerance to paternal genotoxic damage promotes survival during embryo development in zebrafish (Danio rerio)Cristina Fernández-Díez0Silvia González-Rojo1Marta Lombó2M. Paz Herráez3 Department of Molecular Biology, Faculty of Biology, Universidad de León, Campus de Vegazana, s/n 24071, León, Spain Department of Molecular Biology, Faculty of Biology, Universidad de León, Campus de Vegazana, s/n 24071, León, Spain Department of Molecular Biology, Faculty of Biology, Universidad de León, Campus de Vegazana, s/n 24071, León, Spain Department of Molecular Biology, Faculty of Biology, Universidad de León, Campus de Vegazana, s/n 24071, León, Spain Spermatozoa carry DNA damage that must be repaired by the oocyte machinery upon fertilization. Different strategies could be adopted by different vertebrates to face the paternal genotoxic damage. Mammals have strong sperm selection mechanisms and activate a zygotic DNA damage response (DDR) (including cell cycle arrest, DNA repair and alternative apoptosis) in order to guarantee the genomic conformity of the reduced progeny. However, external fertilizers, with different reproductive strategies, seem to proceed distinctively. Previous results from our group showed a downregulation of apoptotic activity in trout embryos with a defective DNA repairing ability, suggesting that mechanisms of tolerance to damaged DNA could be activated in fish to maintain cell survival and to progress with development. In this work, zebrafish embryos were obtained from control or UV-irradiated sperm (carrying more than 10% of fragmented DNA but still preserving fertilization ability). DNA repair (γH2AX and 53BP1 foci), apoptotic activity, expression of genes related to DDR and malformation rates were analyzed throughout development. Results showed in the progeny from damaged sperm, an enhanced repairing activity at the mid-blastula transition stage that returned to its basal level at later stages, rendering at hatching a very high rate of multimalformed larvae. The study of transcriptional and post-translational activity of tp53 (ZDF-GENE-990415-270) revealed the activation of an intense DDR in those progenies. However, the downstream pro-apoptotic factor noxa (ZDF-GENE-070119-3) showed a significant downregulation, whereas the anti-apoptotic gene bcl2 (ZDF-GENE-051015-1) was upregulated, triggering a repressive apoptotic scenario in spite of a clear genomic instability. This repression can be explained by the observed upregulation of p53 isoform Δ113p53, which is known to enhance bcl2 transcription. Our results showed that tp53 is involved in DNA damage tolerance (DDT) pathways, allowing the embryo survival regardless of the paternal DNA damage. DDT could be an evolutionary mechanism in fish: tolerance to unrepaired sperm DNA could introduce new mutations, some of them potentially advantageous to face a changing environment.http://bio.biologists.org/content/7/5/bio030130DNA damage responseDNA damage toleranceDNA repairEmbryo developmentSperm DNA damage |
| spellingShingle | Cristina Fernández-Díez Silvia González-Rojo Marta Lombó M. Paz Herráez Tolerance to paternal genotoxic damage promotes survival during embryo development in zebrafish (Danio rerio) Biology Open DNA damage response DNA damage tolerance DNA repair Embryo development Sperm DNA damage |
| title | Tolerance to paternal genotoxic damage promotes survival during embryo development in zebrafish (Danio rerio) |
| title_full | Tolerance to paternal genotoxic damage promotes survival during embryo development in zebrafish (Danio rerio) |
| title_fullStr | Tolerance to paternal genotoxic damage promotes survival during embryo development in zebrafish (Danio rerio) |
| title_full_unstemmed | Tolerance to paternal genotoxic damage promotes survival during embryo development in zebrafish (Danio rerio) |
| title_short | Tolerance to paternal genotoxic damage promotes survival during embryo development in zebrafish (Danio rerio) |
| title_sort | tolerance to paternal genotoxic damage promotes survival during embryo development in zebrafish danio rerio |
| topic | DNA damage response DNA damage tolerance DNA repair Embryo development Sperm DNA damage |
| url | http://bio.biologists.org/content/7/5/bio030130 |
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