Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Cancer Center, First Hospital of Jilin University, Changchun 130061, China.
Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
Cells. 2022 Oct 5;11(19):3130. doi: 10.3390/cells11193130.
Recurrent spontaneous abortion (RSA) is a highly heterogeneous complication of pregnancy with the underlying mechanisms remaining uncharacterized. Dysregulated decidualization is a critical contributor to the phenotypic alterations related to pregnancy complications. To understand the molecular factors underlying RSA, we explored the role of longnoncoding RNAs (lncRNAs) in the decidual microenvironment where the crosstalk at the fetal-maternal interface occurs. By exploring RNA-seq data from RSA patients, we identified , a noncoding RNA that exhibits maternal monoallelic expression, as one of the most upregulated lncRNAs associated with RSA. The paternally expressed fetal mitogen which is reciprocally coregulated with within the same imprinting cluster, was also upregulated. Notably, both genes underwent loss of imprinting, as and were actively transcribed from both parental alleles in some decidual tissues. This loss of imprinting in decidual tissues was associated with the loss of the H3K27m3 repressive histone marker in the promoter, CpG hypomethylation at the central CTCF binding site in the imprinting control center (ICR), and the loss of CTCF-mediated intrachromosomal looping. These data suggest that dysregulation of the imprinting pathway may be an important epigenetic factor in the decidual microenvironment related to poor decidualization.
复发性自然流产（RSA）是一种高度异质性的妊娠并发症，其潜在机制尚不清楚。蜕膜化失调是与妊娠并发症相关的表型改变的重要贡献者。为了了解 RSA 背后的分子因素，我们探讨了长非编码 RNA（lncRNA）在蜕膜微环境中的作用，胎儿-母体界面的串扰发生在该环境中。通过探索来自 RSA 患者的 RNA-seq 数据，我们确定了 ，一种表现出母体单等位基因表达的非编码 RNA，是与 RSA 相关的上调最显著的 lncRNA 之一。与 在同一印记簇中相互反向调节的父系表达的胎儿有丝分裂原 也被上调。值得注意的是，这两个基因都发生了印记丢失，因为 在一些蜕膜组织中，从两个亲本等位基因都被主动转录。这种蜕膜组织中的印记丢失与 启动子中 H3K27m3 抑制性组蛋白标记的丢失、印记控制中心（ICR）中中央 CTCF 结合位点的 CpG 低甲基化以及 CTCF 介导的染色体内环looping 的丢失有关。这些数据表明，印迹途径的失调可能是与不良蜕膜化相关的蜕膜微环境中的一个重要表观遗传因素。
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