Department of Human Physiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, Warszawska Str 30, 10-082 Olsztyn, Poland.
Department of Gynecology and Obstetrics, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, Niepodleglosci Str 44, 10-045 Olsztyn, Poland.
Int J Mol Sci. 2019 Mar 26;20(6):1510. doi: 10.3390/ijms20061510.
Intrauterine growth restriction (IUGR) is a serious pathological complication associated with compromised fetal development during pregnancy. The aim of the study was to broaden knowledge about the transcriptomic complexity of the human placenta by identifying genes potentially involved in IUGR pathophysiology. RNA-Seq data were used to profile protein-coding genes, detect alternative splicing events (AS), single nucleotide variant (SNV) calling, and RNA editing sites prediction in IUGR-affected placental transcriptome. The applied methodology enabled detection of 37,501 transcriptionally active regions and the selection of 28 differentially-expressed genes (DEGs), among them 10 were upregulated and 18 downregulated in IUGR-affected placentas. Functional enrichment annotation indicated that most of the DEGs were implicated in the processes of inflammation and immune disorders related to IUGR and preeclampsia. Additionally, we revealed that some genes (, , , and ) involved in the alternation of splicing events were mainly implicated in angiogenic-related processes. Significant SNVs were overlapped with 6533 transcripts and assigned to 2386 coding sequence (CDS), 1528 introns, 345 5' untranslated region (UTR), 1260 3'UTR, 918 non-coding RNA (ncRNA), and 10 intergenic regions. Within CDS regions, 543 missense substitutions with functional effects were recognized. Two known mutations (rs4575, synonymous; rs3817, on the downstream region) were detected within the range of AS and DEG candidates: and , respectively. Novel genes that are dysregulated in IUGR were detected in the current research. Investigating genes underlying the IUGR is crucial for identification of mechanisms regulating placental development during a complicated pregnancy.
胎儿宫内生长受限（IUGR）是一种严重的病理并发症，与妊娠期间胎儿发育不良有关。本研究旨在通过鉴定可能与 IUGR 病理生理学相关的基因，来拓宽对人类胎盘转录组复杂性的认识。使用 RNA-Seq 数据对受 IUGR 影响的胎盘转录组中的蛋白质编码基因进行了分析，检测了可变剪接事件（AS）、单核苷酸变异（SNV）调用和 RNA 编辑位点预测。所应用的方法能够检测到 37501 个转录活跃区，并选择了 28 个差异表达基因（DEG），其中 10 个在 IUGR 胎盘组织中上调，18 个下调。功能富集注释表明，大多数 DEG 与 IUGR 和子痫前期相关的炎症和免疫紊乱过程有关。此外，我们发现一些参与可变剪接事件改变的基因（、、、和）主要与血管生成相关过程有关。显著的 SNV 与 6533 个转录本重叠，并分配给 2386 个编码序列（CDS）、1528 个内含子、345 个 5'非翻译区（UTR）、1260 个 3'UTR、918 个非编码 RNA（ncRNA）和 10 个基因间区。在 CDS 区域内，识别出 543 个具有功能效应的错义取代。在 AS 和 DEG 候选物范围内检测到两个已知突变（rs4575，同义；rs3817，下游区域）：和，分别。本研究检测到在 IUGR 中失调的新基因。研究 IUGR 相关基因对于鉴定调控复杂妊娠期间胎盘发育的机制至关重要。
