克隆哺乳动物的胎盘发育缺陷.pdfVIP

Hereditas (Beijing) 2016 年 5 月, 38(5): 402―410 综 述 克隆哺乳动物的胎盘发育缺陷 敖政，刘德武，蔡更元，吴珍芳，李紫聪 510642 摘要: 克隆又称体细胞核移植(Somatic cell nuclear transfer, SCNT) ，该技术已在多种哺乳动物中成功建立并被 逐渐应用。然而，利用该技术获得的哺乳动物克隆胚胎的发育效率非常低(一般只有1%~5%)，这严重限制了克 隆技术的应用。胎盘发育缺陷被认为是抑制克隆胚胎发育的一个主要原因。几乎所有的SCNT 来源胎盘都会出 现不同的发育缺陷，如胎盘增生、胎盘血管缺陷、脐带畸形等。胎盘异常的根本原因是滋养层细胞基因组在发 育过程中未能建立正确的表观遗传修饰，导致胎盘发育调控相关的重要基因，特别是印迹基因的表达出现异常。 印迹基因表达异常导致胎盘的形态异常和功能缺陷，进而影响克隆胚胎的发育能力。目前，虽然有许多提高克 隆胚胎发育能力的研究报道，然而在大多数研究中克隆效率并没有得到大幅度的提高，主要原因之一是克隆胚 胎的胎盘发育仍然存在诸多缺陷。本文综述了克隆哺乳动物的胎盘异常及其印迹基因表达，并对未来提高克隆 效率的研究提出展望。 关键词: 体细胞核移植；克隆；表观重编程；胎盘异常；印迹基因 Placental developmental defects in cloned mammalian animals Zheng Ao, Dewu Liu, Gengyuan Cai, Zhenfang Wu, Zicong Li National Engineering Research Center for Swine Breeding Industry, College of Animal Science, South China Agricultural Univer- sity, Guangzhou 510642, China Abstract: The cloning technique, also called somatic cell nuclear transfer(SCNT), has been successfully estab- lished and gradually applied to various mammalian species. However, the developmental rate of SCNT mammalian embryos is very low, usually at 1% to 5%, which limits the application of SCNT. Placental developmental defects are considered as the main cause of SCNT embryo development inhibition. Almost all of SCNT-derived mammalian placentas exhibit various abnormalities, such as placental hyperplasia, vascular defects and umbilical cord malforma- tion. Mechanistically, these abnormalities result from failure of establishment of correct epigenetic modification in the trophectoderm genome, which leads to erroneous expression of important genes for placenta development-related, particularly imprinted genes. Consequently, aberrant imprinted gene expression gives rise to placental morphologic abnormalities and functional defects, ther