Spatial Transcriptomic and miRNA Analyses Revealed Genes Involved in the Mesometrial-Biased Implantation in Pigs

Spatial Transcriptomic and miRNA Analyses Revealed Genes Involved in the Mesometrial-Biased Implantation in Pigs
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空间转录组和 miRNA 分析揭示了参与猪系膜偏向着床的基因

DOI:
10.3390/genes10100808
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发表时间:
2019-10-01
期刊:
影响因子:
3.5
通讯作者:
Yu, Mei
Yu, Mei
中科院分区:
生物学3区
文献类型:
--
作者:
Huang, Ji;Yang, Yifen;Yu, Mei

文献摘要

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着床失败是早期胚胎丢失的主要原因。通常情况下,妊娠附着起始于子宫系膜侧,然后扩散到子宫反系膜侧,然而,指导系膜偏向附着的机制在很大程度上是未知的。在这项研究中,从妊娠12天(前附着阶段)和15天(后附着阶段)的整个子宫横截面的组织学特征进行了研究,并观察子宫系膜侧和反系膜侧之间的组织学特征的差异。然后,分别对从妊娠第12天和第15天获得的子宫系膜和反系膜子宫内膜进行转录组学和miRNA分析。差异表达基因(DEG)和微RNA(DE-miR),共同的或独特的两个解剖位置的子宫分别进行了鉴定,表明在分子上的差异反应植入孕体之间存在的两个解剖位置。此外,我们分别在两个妊娠日的两个解剖位置之间检测DEG和DE-miR。在这些DEG中,发现许多基因,如趋化因子和T细胞表面标记基因,在子宫系膜中显著上调。此外,我们还采用双荧光素酶报告基因检测了CXCR 4、CXCL 11和miR-9之间的相互作用。总之,这项研究揭示了可能在子宫系膜侧创造一个接受性微环境的基因和途径,这是指导猪子宫内孕体正确定位所必需的。
Implantation failure is a major cause of early embryonic loss. Normally, the conceptus attachment is initiated at mesometrial side of the uterus and then spread to the anti-mesometrial side in pigs, however, the mechanisms that direct the mesometrial-biased attachment are largely unknown. In this study, the histological features of the entire uterine cross-section from gestational days 12 (pre-attachment stage) and 15 (post-attachment stage) were investigated and the differences in histological features between the mesometrial and anti-mesometrial side of the uterus were observed. Then, transcriptomic and miRNA analyses were performed on mesometrial and anti-mesometrial endometrium obtained from gestational days 12 and 15, respectively. Differentially expressed genes (DEGs) and miRNAs (DE-miRs) that were common to both or unique to either of the two anatomical locations of uterus were identified, respectively, indicating that differences in molecular response to the implanting conceptus exist between the two anatomical locations. In addition, we detected DEGs and DE-miRs between the two anatomical locations on the two gestational days, respectively. Of these DEGs, a number of genes, such as chemokine and T cell surface marker genes, were found to be significantly up-regulated mesometrially. Furthermore, we detected the interaction of CXCR4, CXCL11 and miR-9 using dual luciferase reporter assay. Taken together, this study revealed genes and pathways that might play the role of creating a receptive microenvironment at the mesometrial side, which is required to guide a proper positioning of conceptus in the uterus in pigs.