克隆哺乳动物的胎盘发育缺陷

Placental developmental defects in cloned mammalian animals

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。

The cloning technique, also called somatic cell nuclear transfer（SCNT）, has been successfully established 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 malformation. 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, therefore decreases developmental competence of cloned＆nbsp;embryos. Currently, although numerous methods that can improve the developmental ability of SCNT-derived embryos have been reported, most of them are unable to substantially enhance the success rate of SCNT due to failure to eliminate the placental development defects. In this review, we summarize placental abnormalities and imprinted gene expression in mammalian cloning, and propose directions for the future research aiming to improve the cloning efficiency.