Resveratrol improved the developmental potential of oocytes after vitrification by modifying the epigenetics

Abstract

Resveratrol (Res) has been reported to be able to improve oocyte vitrification because of its antioxidative properties. The objective of this study was to further assess the positive effect of Res addition on the developmental potential of vitrified mouse oocytes from the perspective of epigenetic alterations. First, 2 μM Res was chosen as the optimal concentration on the basis of its effects on survival and its antioxidative properties. We found that Res addition significantly promoted fertilization (63.8% vs. 42.9%) and blastocyst formation (68.3% vs. 50.2%) after oocyte vitrification. The quality of the derived blastocysts was also higher after Res treatment. Regarding epigenetic aspects, the expression of the important deacetylase SIRT1 was found to decrease significantly upon vitrification, but it was rescued by Res. The abnormal levels of H3K9 acetylation and DNA methylation in vitrified oocytes were restored by Res addition. Moreover, the expression of several imprinted genes was affected by oocyte vitrification. Among them, abnormal Gtl2 and Peg3 expression levels were restored by Res addition. Therefore, the methylation of their imprinted control regions (ICRs) was examined. Surprisingly, the abnormal patterns of Gtl2 and Peg3 methylation in blastocysts developed from vitrified oocytes were both restored by Res addition. Finally, the full‐term embryonic development showed that the birth rate was improved significantly by Res addition (56.2% vs. 38.1%). Collectively, Res was beneficial for the pre‐ and postimplantation embryonic development. Except for the antioxidative activity, Res also played a role in the correction of some abnormal epigenetic modifications caused by oocyte vitrification.

Effect of oocyte vitrification on DNA damage in metaphase II oocytes and the resulting preimplantation embryos

“…The aberrant accumulation of DSBs that are not repaired in time might give rise to apoptosis (Roos & Kaina, ). Our previous results indicated that bovine oocyte vitrification could induce apoptosis in blastocysts (Chen et al, ). Many other studies also showed that oocyte vitrification could increase apoptosis in blastocysts (Dai et al, ; Zhao et al, ), which was in line with our results.…”

“…These results imply that the accumulation of DSBs might, at least in part, contribute to the increased apoptotic rate in blastocysts. Chen et al () found that resveratrol treatment could decrease vitrification‐induced apoptosis. This was consistent with our results.…”

“…Western blot analysis was carried out as previously described, with minor modifications (Chen et al, ). A total of 150 MII oocytes or 150 embryos per pool were lysed using RIPA buffer (Beyotime Inst.…”

What impact does oocyte vitrification have on epigenetics and gene expression?

“…2 Epigenetic effects of oocyte vitrification in humans and animals (a global overview). Numbers in brackets mean the number of studies reporting differences out of the total number of studies in the literature consistently reported (Table 4) [113,114,[129][130][131]133]. However, Chen et al recently reported an upregulation of two imprinted genes that are known to play a crucial role in development (Gtl2 and Peg10 ) [130].…”

“…When the analyses focused specifically on genes involved in epigenetic modifications, a significant downregulation of gene expression after vitrification has been consistently reported (Table 4 ) [ 113 , 114 , 129 – 131 , 133 ]. However, Chen et al recently reported an upregulation of two imprinted genes that are known to play a crucial role in development ( Gtl2 and Peg10 ) [ 130 ].…”