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DNA Double Strand Breaks but Not Interstrand Crosslinks Prevent Progress through Meiosis in Fully Grown Mouse Oocytes
There is some interest in how mammalian oocytes respond to different types of DNA damage because of the increasing expectation of fertility preservation in women undergoing chemotherapy. Double strand breaks (DSBs) induced by ionizing radiation and agents such as neocarzinostatin (NCS), and interstr...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3425511/ https://www.ncbi.nlm.nih.gov/pubmed/22928046 http://dx.doi.org/10.1371/journal.pone.0043875 |
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author | Yuen, Wai Shan Merriman, Julie A. O'Bryan, Moira K. Jones, Keith T |
author_facet | Yuen, Wai Shan Merriman, Julie A. O'Bryan, Moira K. Jones, Keith T |
author_sort | Yuen, Wai Shan |
collection | PubMed |
description | There is some interest in how mammalian oocytes respond to different types of DNA damage because of the increasing expectation of fertility preservation in women undergoing chemotherapy. Double strand breaks (DSBs) induced by ionizing radiation and agents such as neocarzinostatin (NCS), and interstrand crosslinks (ICLs) induced by alkylating agents such as mitomycin C (MMC), are toxic DNA lesions that need to be repaired for cell survival. Here we examined the effects of NCS and MMC treatment on oocytes collected from antral follicles in mice, because potentially such oocytes are readily collected from ovaries and do not need to be in vitro grown to achieve meiotic competency. We found that oocytes were sensitive to NCS, such that this ionizing radiation mimetic blocked meiosis I and caused fragmented DNA. In contrast, MMC had no impact on the completion of either meiosis I or II, even at extremely high doses. However, oocytes treated with MMC did show γ-H2AX foci and following their in vitro maturation and parthenogenetic activation the development of the subsequent embryos was severely compromised. Addition of MMC to 1-cell embryos caused a similarly poor level of development, demonstrating oocytes have eventual sensitivity to this ICL-inducing agent but this does not occur during their meiotic division. In oocytes, the association of Fanconi Anemia protein, FANCD2, with sites of ICL lesions was not apparent until entry into the embryonic cell cycle. In conclusion, meiotic maturation of oocytes is sensitive to DSBs but not ICLs. The ability of oocytes to tolerate severe ICL damage and yet complete meiosis, means that this type of DNA lesion goes unrepaired in oocytes but impacts on subsequent embryo quality. |
format | Online Article Text |
id | pubmed-3425511 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34255112012-08-27 DNA Double Strand Breaks but Not Interstrand Crosslinks Prevent Progress through Meiosis in Fully Grown Mouse Oocytes Yuen, Wai Shan Merriman, Julie A. O'Bryan, Moira K. Jones, Keith T PLoS One Research Article There is some interest in how mammalian oocytes respond to different types of DNA damage because of the increasing expectation of fertility preservation in women undergoing chemotherapy. Double strand breaks (DSBs) induced by ionizing radiation and agents such as neocarzinostatin (NCS), and interstrand crosslinks (ICLs) induced by alkylating agents such as mitomycin C (MMC), are toxic DNA lesions that need to be repaired for cell survival. Here we examined the effects of NCS and MMC treatment on oocytes collected from antral follicles in mice, because potentially such oocytes are readily collected from ovaries and do not need to be in vitro grown to achieve meiotic competency. We found that oocytes were sensitive to NCS, such that this ionizing radiation mimetic blocked meiosis I and caused fragmented DNA. In contrast, MMC had no impact on the completion of either meiosis I or II, even at extremely high doses. However, oocytes treated with MMC did show γ-H2AX foci and following their in vitro maturation and parthenogenetic activation the development of the subsequent embryos was severely compromised. Addition of MMC to 1-cell embryos caused a similarly poor level of development, demonstrating oocytes have eventual sensitivity to this ICL-inducing agent but this does not occur during their meiotic division. In oocytes, the association of Fanconi Anemia protein, FANCD2, with sites of ICL lesions was not apparent until entry into the embryonic cell cycle. In conclusion, meiotic maturation of oocytes is sensitive to DSBs but not ICLs. The ability of oocytes to tolerate severe ICL damage and yet complete meiosis, means that this type of DNA lesion goes unrepaired in oocytes but impacts on subsequent embryo quality. Public Library of Science 2012-08-22 /pmc/articles/PMC3425511/ /pubmed/22928046 http://dx.doi.org/10.1371/journal.pone.0043875 Text en © 2012 Yuen et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Yuen, Wai Shan Merriman, Julie A. O'Bryan, Moira K. Jones, Keith T DNA Double Strand Breaks but Not Interstrand Crosslinks Prevent Progress through Meiosis in Fully Grown Mouse Oocytes |
title | DNA Double Strand Breaks but Not Interstrand Crosslinks Prevent Progress through Meiosis in Fully Grown Mouse Oocytes |
title_full | DNA Double Strand Breaks but Not Interstrand Crosslinks Prevent Progress through Meiosis in Fully Grown Mouse Oocytes |
title_fullStr | DNA Double Strand Breaks but Not Interstrand Crosslinks Prevent Progress through Meiosis in Fully Grown Mouse Oocytes |
title_full_unstemmed | DNA Double Strand Breaks but Not Interstrand Crosslinks Prevent Progress through Meiosis in Fully Grown Mouse Oocytes |
title_short | DNA Double Strand Breaks but Not Interstrand Crosslinks Prevent Progress through Meiosis in Fully Grown Mouse Oocytes |
title_sort | dna double strand breaks but not interstrand crosslinks prevent progress through meiosis in fully grown mouse oocytes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3425511/ https://www.ncbi.nlm.nih.gov/pubmed/22928046 http://dx.doi.org/10.1371/journal.pone.0043875 |
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