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...

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Autores principales:	Wai Shan Yuen, Julie A Merriman, Moira K O'Bryan, Keith T Jones
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3111bf98757e4f12b0474ea4fe5d8f61
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spelling	oai:doaj.org-article:3111bf98757e4f12b0474ea4fe5d8f612021-11-18T07:07:57ZDNA double strand breaks but not interstrand crosslinks prevent progress through meiosis in fully grown mouse oocytes.1932-620310.1371/journal.pone.0043875https://doaj.org/article/3111bf98757e4f12b0474ea4fe5d8f612012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22928046/?tool=EBIhttps://doaj.org/toc/1932-6203There 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.Wai Shan YuenJulie A MerrimanMoira K O'BryanKeith T JonesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e43875 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wai Shan Yuen Julie A Merriman Moira K O'Bryan Keith T Jones DNA double strand breaks but not interstrand crosslinks prevent progress through meiosis in fully grown mouse oocytes.
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	article
author	Wai Shan Yuen Julie A Merriman Moira K O'Bryan Keith T Jones
author_facet	Wai Shan Yuen Julie A Merriman Moira K O'Bryan Keith T Jones
author_sort	Wai Shan Yuen
title	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_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_sort	dna double strand breaks but not interstrand crosslinks prevent progress through meiosis in fully grown mouse oocytes.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/3111bf98757e4f12b0474ea4fe5d8f61
work_keys_str_mv	AT waishanyuen dnadoublestrandbreaksbutnotinterstrandcrosslinkspreventprogressthroughmeiosisinfullygrownmouseoocytes AT julieamerriman dnadoublestrandbreaksbutnotinterstrandcrosslinkspreventprogressthroughmeiosisinfullygrownmouseoocytes AT moirakobryan dnadoublestrandbreaksbutnotinterstrandcrosslinkspreventprogressthroughmeiosisinfullygrownmouseoocytes AT keithtjones dnadoublestrandbreaksbutnotinterstrandcrosslinkspreventprogressthroughmeiosisinfullygrownmouseoocytes
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DNA double strand breaks but not interstrand crosslinks prevent progress through meiosis in fully grown mouse oocytes.

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