Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/95840
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Type: Journal article
Title: DNA double strand breaks but not interstrand crosslinks prevent progress through meiosis in fully grown mouse oocytes
Author: Yuen, W.
Merriman, J.
O'Bryan, M.
Jones, K.
Citation: PLoS One, 2012; 7(8):e43875-1-e43875-9
Publisher: Public Library of Science
Issue Date: 2012
ISSN: 1932-6203
1932-6203
Statement of
Responsibility: 
Wai Shan Yuen, Julie A. Merriman, Moira K. O’Bryan, Keith T. Jones
Abstract: 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.
Keywords: Oocytes
Rights: © Yuen et al. 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 credited.
RMID: 0030036166
DOI: 10.1371/journal.pone.0043875
Appears in Collections:Medicine publications

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