Abstract
Objective
Successful oocyte vitrification (OV) is critical for cryopreservation of the oocytes from female patients with infertility, polycystic ovaries, and gynecologic cancers. Recent evidence suggests that relatively low levels of histone acetylation are critical for maintenance of the maturation capacity of cryopreserved oocytes. However, previous studies have only demonstrated a key role of histone deacetylases (HDAC) 1 and 2 in the cryopreservation of oocytes.
Methods
In this study, we investigated the role of HDAC6 in these settings. We found that mouse oocytes with low HDAC6 levels decreased survival rate, cleavage rate, and blastocyst rate after OV. Bioinformatics analyses were used to predict HDAC6-targeting microRNAs (miRNAs), while the functional binding of miRNAs to HDAC6 mRNA was evaluated by a dual luciferase reporter assay.
Results
Among all HDAC6-targeting miRNAs, we detected expression of miR-558, miR-527, and miR-762 in mouse oocytes. Specifically, we found that only miR-762 significantly inhibited protein translation of HDAC6 via binding to the 3′-UTR of the HDAC6 mRNA. Transfection of oocytes with HDAC6 or antisense of miR-762 significantly increased the survival rate, the cleavage rate, and blastocyst rate after OV.
Conclusion
As a result, our data suggest that induction of HDAC6 levels by miR-762 suppression may improve the current protocol for OV.
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References
Saragusty J, Arav A. Current progress in oocyte and embryo cryopreservation by slow freezing and vitrification. Reproduction. 2011;141:1–19.
Martin C, Zhang Y. Mechanisms of epigenetic inheritance. Curr Opin Cell Biol. 2007;19:266–72.
Ma P, Pan H, Montgomery RL, Olson EN, Schultz RM. Compensatory functions of histone deacetylase 1 (HDAC1) and HDAC2 regulate transcription and apoptosis during mouse oocyte development. Proc Natl Acad Sci U S A. 2012;109:E481–9.
Boyault C, Sadoul K, Pabion M, Khochbin S. HDAC6, at the crossroads between cytoskeleton and cell signaling by acetylation and ubiquitination. Oncogene. 2007;26:5468–76.
Zhu P, Zhang J, Zhu J, Shi J, Zhu Q, Gao Y. MiR-429 induces gastric carcinoma cell apoptosis through Bcl-2. Cell Physiol Biochem. 2015;37:1572–80.
Zhang T, Tian F, Wang J, Jing J, Zhou SS, Chen YD. Atherosclerosis-associated endothelial cell apoptosis by MiR-429-mediated down regulation of Bcl-2. Cell Physiol Biochem. 2015;37:1421–30.
Sun DK, Wang JM, Zhang P, Wang YQ. MicroRNA-138 regulates metastatic potential of bladder cancer through ZEB2. Cell Physiol Biochem. 2015;37:2366–74.
Song W, Li Q, Wang L, Wang L. Modulation of FoxO1 expression by miR-21 to promote growth of pancreatic ductal adenocarcinoma. Cell Physiol Biochem. 2015;35:184–90.
Bae HJ, Jung KH, Eun JW, Shen Q, Kim HS, Park SJ, et al. MicroRNA-221 governs tumor suppressor HDAC6 to potentiate malignant progression of liver cancer. J Hepatol. 2015;63:408–19.
Lee SW, Yang J, Kim SY, Jeong HK, Lee J, Kim WJ, et al. MicroRNA-26a induced by hypoxia targets HDAC6 in myogenic differentiation of embryonic stem cells. Nucleic Acids Res. 2015;43:2057–73.
Wang Y, Okitsu O, Zhao XM, Sun Y, Di W, Chian RC. The effect of minimal concentration of ethylene glycol (EG) combined with polyvinylpyrrolidone (PVP) on mouse oocyte survival and subsequent embryonic development following vitrification. J Assist Reprod Genet. 2014;31:55–63.
Xu Y, Zhou T, Shao L, Zhang B, Liu K, Gao C, et al. Gene expression profiles in mouse cumulus cells derived from in vitro matured oocytes with and without blastocyst formation. Gene Expr Patterns. 2017;25-26:46–58.
Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. Elife. 2015;4
He JC, Yao W, Wang JM, Schemmer P, Yang Y, Liu Y, et al. TACC3 overexpression in cholangiocarcinoma correlates with poor prognosis and is a potential anti-cancer molecular drug target for HDAC inhibitors. Oncotarget. 2016;7:75441–56.
Bahr JC, Robey RW, Luchenko V, Basseville A, Chakraborty AR, Kozlowski H, et al. Blocking downstream signaling pathways in the context of HDAC inhibition promotes apoptosis preferentially in cells harboring mutant Ras. Oncotarget. 2016;7:69804–15.
Cao Z, Wu R, Gao D, Xu T, Luo L, Li Y, et al. Maternal histone acetyltransferase KAT8 is required for porcine preimplantation embryo development. Oncotarget. 2017;8(52):90250–61.
Marinho LSR, Rissi VB, Lindquist AG, Seneda MM, Bordignon V, et al. Acetylation and methylation profiles of H3K27 in porcine embryos cultured in vitro. Zygote. 2017;25(5):575–82.
Ma P, Schultz RM. HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: specificity versus compensation. Cell Death Differ. 2016;23(7):1119–27.
Funding
The research was supported by the Chinese National Natural Science foundation (81401263), Shanghai municipal health and Family Planning Commission of traditional Chinese medicine research (2014LP010A), Research project of Shanghai municipal health and Family Planning Commission (140826110504864), and Shanghai Jiao University Scientific and Technological Innovation Funds (17JCYA01).
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Wang, Y., Zhang, Ml., Zhao, Lw. et al. Enhancement of the efficiency of oocyte vitrification through regulation of histone deacetylase 6 expression. J Assist Reprod Genet 35, 1179–1185 (2018). https://doi.org/10.1007/s10815-018-1221-6
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DOI: https://doi.org/10.1007/s10815-018-1221-6