通过调控组蛋白去乙酰化酶 6 的表达来提高卵母细胞玻璃化冷冻的效率。
Enhancement of the efficiency of oocyte vitrification through regulation of histone deacetylase 6 expression.
机构信息
Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai, 200011, China.
Center of Reproductive Medicine, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200135, China.
出版信息
J Assist Reprod Genet. 2018 Jul;35(7):1179-1185. doi: 10.1007/s10815-018-1221-6. Epub 2018 Jul 4.
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.
目的
卵母细胞玻璃化（OV）的成功对于保存患有不孕、多囊卵巢和妇科癌症的女性患者的卵母细胞至关重要。最近的证据表明，相对较低水平的组蛋白乙酰化对于维持冷冻保存卵母细胞的成熟能力至关重要。然而，以前的研究仅表明组蛋白去乙酰化酶（HDAC）1 和 2 在卵母细胞的冷冻保存中起关键作用。
方法
在这项研究中，我们研究了 HDAC6 在这些情况下的作用。我们发现，HDAC6 水平较低的小鼠卵母细胞在 OV 后存活率、分裂率和囊胚率降低。生物信息学分析用于预测 HDAC6 靶向 microRNAs（miRNAs），而通过双荧光素酶报告基因测定评估 miRNA 与 HDAC6 mRNA 的功能结合。
结果
在所有 HDAC6 靶向 miRNAs 中，我们在小鼠卵母细胞中检测到 miR-558、miR-527 和 miR-762 的表达。具体而言，我们发现只有 miR-762 通过结合 HDAC6 mRNA 的 3'UTR 显著抑制 HDAC6 的蛋白质翻译。用 HDAC6 或 miR-762 的反义转染卵母细胞可显著提高 OV 后的存活率、分裂率和囊胚率。
结论
因此，我们的数据表明，通过抑制 miR-762 诱导 HDAC6 水平可能会改善当前的 OV 方案。
Zotero 插件