Yuan Shuiqiao, Schuster Andrew, Tang Chong, Yu Tian, Ortogero Nicole, Bao Jianqiang, Zheng Huili, Yan Wei
Department of Physiology and Cell Biology, University of Nevada School of Medicine, 1664 North Virginia Street, MS 0575, Reno, NV 89557, USA.
Department of Physiology and Cell Biology, University of Nevada School of Medicine, 1664 North Virginia Street, MS 0575, Reno, NV 89557, USA
Development. 2016 Feb 15;143(4):635-47. doi: 10.1242/dev.131755. Epub 2015 Dec 30.
Although it is believed that mammalian sperm carry small noncoding RNAs (sncRNAs) into oocytes during fertilization, it remains unknown whether these sperm-borne sncRNAs truly have any function during fertilization and preimplantation embryonic development. Germline-specific Dicer and Drosha conditional knockout (cKO) mice produce gametes (i.e. sperm and oocytes) partially deficient in miRNAs and/or endo-siRNAs, thus providing a unique opportunity for testing whether normal sperm (paternal) or oocyte (maternal) miRNA and endo-siRNA contents are required for fertilization and preimplantation development. Using the outcome of intracytoplasmic sperm injection (ICSI) as a readout, we found that sperm with altered miRNA and endo-siRNA profiles could fertilize wild-type (WT) eggs, but embryos derived from these partially sncRNA-deficient sperm displayed a significant reduction in developmental potential, which could be rescued by injecting WT sperm-derived total or small RNAs into ICSI embryos. Disrupted maternal transcript turnover and failure in early zygotic gene activation appeared to associate with the aberrant miRNA profiles in Dicer and Drosha cKO spermatozoa. Overall, our data support a crucial function of paternal miRNAs and/or endo-siRNAs in the control of the transcriptomic homeostasis in fertilized eggs, zygotes and two-cell embryos. Given that supplementation of sperm RNAs enhances both the developmental potential of preimplantation embryos and the live birth rate, it might represent a novel means to improve the success rate of assisted reproductive technologies in fertility clinics.
尽管人们认为哺乳动物的精子在受精过程中将小非编码RNA（sncRNAs）带入卵母细胞，但这些精子携带的sncRNAs在受精和植入前胚胎发育过程中是否真的具有任何功能仍不清楚。生殖系特异性Dicer和Drosha条件性敲除（cKO）小鼠产生的配子（即精子和卵母细胞）部分缺乏miRNA和/或内源性siRNA，从而为测试正常精子（父本）或卵母细胞（母本）的miRNA和内源性siRNA含量是否是受精和植入前发育所必需的提供了独特的机会。以胞浆内单精子注射（ICSI）的结果作为读数，我们发现miRNA和内源性siRNA谱改变的精子可以使野生型（WT）卵子受精，但来自这些部分sncRNA缺陷精子的胚胎显示出发育潜力显著降低，通过将WT精子来源的总RNA或小RNA注射到ICSI胚胎中可以挽救这种情况。母源转录本周转的破坏和早期合子基因激活的失败似乎与Dicer和Drosha cKO精子中异常的miRNA谱有关。总体而言，我们的数据支持父本miRNA和/或内源性siRNA在控制受精卵、合子和二细胞胚胎的转录组稳态中起关键作用。鉴于补充精子RNA可提高植入前胚胎的发育潜力和活产率，这可能代表了一种提高生育诊所辅助生殖技术成功率的新方法。
