Sui Linlin, An Lei, Tan Kun, Wang Zhuqing, Wang Shumin, Miao Kai, Ren Likun, Tao Li, He Shuzhi, Yu Yong, Nie Jinzhou, Liu Qian, Xing Lei, Wu Zhonghong, Hou Zhuocheng, Tian Jianhui
Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Sciences and Technology, China Agricultural University, Haidian, Beijing, China.
BGI Tech Solutions Co., Ltd., Beishan Industrial Zone, Shenzhen, China.
Biol Reprod. 2014 Dec;91(6):155. doi: 10.1095/biolreprod.114.124248. Epub 2014 Oct 15.
As the interface between the mother and the developing fetus, the placenta is believed to play an important role in assisted reproductive technology (ART)-induced aberrant intrauterine and postnatal development. However, the mechanisms underlying aberrant placentation remain unclear, especially during extraembryonic tissue development and early stages of placental formation. Using a mouse model, this investigation provides the first comparative proteomic analysis of in vivo (IVO) and in vitro-produced (IVP) extraembryonic tissues and placentas after IVO fertilization and development, or in vitro fertilization and culture, respectively. We identified 165 and 178 differentially expressed proteins (DEPs) between IVO and IVP extraembryonic tissues and placentas on Embryonic Day 7.5 (E7.5) and E10.5, respectively. Many DEPs were functionally associated with genetic information processing, such as impaired de novo DNA methylation, as well as posttranscriptional, translational and posttranslational dysregulation. These novel findings were further confirmed by global hypomethylation, and a lower level of correlation was found between the transcriptome and proteome in the IVP groups. In addition, numerous DEPs were involved in energy and amino acid metabolism, cytoskeleton organization and transport, and vasculogenesis and angiogenesis. These disturbed processes and pathways are likely to be associated with embryonic intrauterine growth restriction, an enlarged placenta, and impaired labyrinth morphogenesis. This study provides a direct and comprehensive reference for the further exploration of the placental mechanisms that underlie ART-induced developmental aberrations.
作为母亲与发育中胎儿之间的界面,胎盘被认为在辅助生殖技术(ART)诱导的子宫内及产后异常发育中起重要作用。然而,胎盘形成异常的潜在机制仍不清楚,尤其是在胚外组织发育和胎盘形成的早期阶段。本研究使用小鼠模型,首次分别对体内(IVO)受精发育或体外受精培养后获得的体内(IVO)和体外产生(IVP)的胚外组织及胎盘进行了比较蛋白质组学分析。我们分别在胚胎第7.5天(E7.5)和E10.5时,鉴定出IVO和IVP胚外组织及胎盘之间有165和178个差异表达蛋白(DEP)。许多DEP在功能上与遗传信息处理相关,如新生DNA甲基化受损,以及转录后、翻译和翻译后失调。这些新发现通过整体低甲基化得到进一步证实,并且在IVP组中发现转录组和蛋白质组之间的相关性较低。此外,大量DEP参与能量和氨基酸代谢、细胞骨架组织与运输,以及血管发生和血管生成。这些受干扰的过程和途径可能与胚胎宫内生长受限、胎盘增大和迷路形态发生受损有关。本研究为进一步探索ART诱导发育异常背后的胎盘机制提供了直接而全面的参考。