Genome transfer for the prevention of female infertility caused by maternal gene mutation
Genome transfer for the prevention of female infertility caused by maternal gene mutation
复制标题
基因组转移用于预防因母体基因突变引起的女性不孕症。
DOI：
10.1016/j.jgg.2020.06.002
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发表时间：
2020-06-20
影响因子：
5.9
通讯作者：
Gao, Shaorong
中科院分区：
文献类型：
--
作者：
Bai, Dandan;Sun, Jin;Gao, Shaorong
卵母细胞质量差与早期胚胎发育停滞和不孕有关。母源基因在卵母细胞成熟调控中起着重要作用，其突变是导致女性不育的常见原因。然而，如何提高卵母细胞的质量和开发有效的治疗母体基因突变仍然是一个难题。在这里，我们使用Zar 1作为一个例子，以评估基因组转移治疗母体基因突变引起的女性不孕症的可行性。我们首先发现，细胞质缺陷主要导致Zar1无效胚胎发育停滞，通过干扰母体转录降解和小合子基因组激活（ZGA）在母合子过渡。接下来，我们在卵母细胞（纺锤体转移或极体转移）和受精卵（早期原核转移或晚期原核转移）阶段进行基因组转移，以验证预防Zar1突变引起的不育的可行性。我们最终证明，无论是在卵母细胞或在早期原核阶段的基因组转移可以支持正常的植入前胚胎发育和生产活的后代。此外，这些幼崽长大成人并显示正常的生育能力。因此，本研究结果为治疗母体基因突变所致女性不孕症提供了有效的治疗依据。中国科学院遗传与发育生物学研究所版权所有（C）2020由爱思唯尔有限公司和科学出版社出版。All rights reserved.
Poor oocyte quality is associated with early embryo developmental arrest and infertility. Maternal gene plays crucial roles in the regulation of oocyte maturation, and its mutation is a common cause of female infertility. However, how to improve oocyte quality and develop effective therapy for maternal gene mutation remains elusive. Here, we use Zar1 as an example to assess the feasibility of genome transfer to cure maternal gene mutation-caused female infertility. We first discover that cytoplasmic deficiency primarily leads to Zar1-null embryo developmental arrest by disturbing maternal transcript degradation and minor zygotic genome activation (ZGA) during the maternal-zygotic transition. We next perform genome transfer at the oocyte (spindle transfer or polar body transfer) and zygote (early pronuclear transfer or late pronuclear transfer) stages to validate the feasibility of preventing Zar1 mutation-caused infertility. We finally demonstrate that genome transfer either at the oocyte or at the early pronuclear stage can support normal preimplantation embryo development and produce live offspring. Moreover, those pups grow to adulthood and show normal fertility. Therefore, our findings provide an effective basis of therapies for the treatment of female infertility caused by maternal gene mutation. Copyright (C) 2020, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.