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Genome transfer for the prevention of female infertility caused by maternal gene mutation.
Journal of Genetics and Genomics ( IF 5.9 ) Pub Date : 2020-06-21 , DOI: 10.1016/j.jgg.2020.06.002
Dandan Bai 1 , Jin Sun 1 , Yanping Jia 1 , Jiqing Yin 1 , Yalin Zhang 1 , Yanhe Li 1 , Rui Gao 1 , Xiling Du 1 , Kunming Li 1 , Jiaming Lin 1 , Zhifen Tu 1 , Yu Wang 1 , Jiaping Pan 1 , Shanshan Liang 1 , Yi Guo 1 , Jingling Ruan 1 , Xiaochen Kou 1 , Yanhong Zhao 1 , Hong Wang 1 , Cizhong Jiang 1 , Fengchao Wang 2 , Xiaoming Teng 1 , Wenqiang Liu 1 , Shaorong Gao 1
Affiliation  

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.



中文翻译:

基因组转移可预防由母体基因突变引起的女性不育。

卵母细胞质量差与早期胚胎发育停滞和不育有关。母体基因在卵母细胞成熟的调控中起着至关重要的作用,其突变是女性不育的常见原因。然而,如何改善卵母细胞的质量并开发有效的母体基因突变疗法仍然遥遥无期。在这里,我们以Zar1为例,评估基因组转移治疗母体基因突变引起的女性不育症的可行性。我们首先发现细胞质缺乏主要导致Zar1-通过扰乱母体-合子过渡期间的母体转录物降解和次要合子基因组激活(ZGA)来使胚胎发育停滞。接下来,我们在卵母细胞(纺锤体转移或极体转移)和合子(早期核转移或晚期核转移)阶段进行基因组转移,以验证预防Zar1突变引起的不育症的可行性。我们最终证明,在卵母细胞或前核早期阶段的基因组转移可以支持正常的植入前胚胎发育并产生活后代。而且,这些幼犬长到成年并显示出正常的生育能力。因此,我们的发现为治疗由母体基因突变引起的女性不育症提供了有效的治疗方法。

更新日期:2020-06-21
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