Roscovitine and Trichostatin A promote DNA damage repair during porcine oocyte maturation
Bingyue Zhang
A , Huiran Niu A , Qingqing Cai A , Mengqin Liao A , Keren Chen A , Yaosheng Chen A and Peiqing Cong A B
+ Author Affiliations
- Author Affiliations
A State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, 510006, PR China.
B Corresponding author. Email: congpq@mail.sysu.edu.cn
Reproduction, Fertility and Development 31(3) 473-481 https://doi.org/10.1071/RD18021
Submitted: 24 November 2017 Accepted: 17 August 2018 Published: 10 October 2018
Abstract
Faithful repair of DNA double-strand breaks in mammalian oocytes is essential for meiotic maturation and embryonic development. In the present study we investigated the roles of Roscovitine and Trichostatin A (TSA) in DNA damage recovery during in vitro maturation of porcine oocytes. Etoposide was used to trigger DNA damage in oocytes. When these DNA-damaged oocytes were treated with 2 μM Roscovitine, 50 nM TSA or both for 22 h, first polar body extrusion and blastocyst formation in all treated groups were significantly improved compared with the etoposide-only group. The most significant improvement was observed when Roscovitine was present. Further immunofluorescent analysis of γH2A.X, an indicator of DNA damage, indicated that DNA damage was significantly decreased in all treated groups. This observation was further supported by analysing the relative mRNA abundance of DNA repair-related genes, including meiotic recombination 11 homolog A (MRE11A), breast cancer type 1 susceptibility protein (BRCA1), Recombinant DNA Repair Protein 51 (RAD51), DNA-dependent protein kinase catalytic subunit (PRKDC) and X-ray cross complementing gene 4 (XRCC4). Compared with the etoposide-only group, the experimental group with combined treatment of Roscovitine and TSA showed a significant decrease of all genes at germinal vesicle and MII stages. The Roscovitine-only treatment group revealed a similar tendency. Together, these results suggest that Roscovitine and TSA treatments could increase the capacity of oocytes to recover from DNA damage by enlisting DNA repair processes.
Additional keywords: CDK2, development, DSBs, HDAC.
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