Department of Gynecology and Obstetrics, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-561 Olsztyn, Poland.
Bioinformatics Core Facility, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland.
Cells. 2021 Apr 16;10(4):921. doi: 10.3390/cells10040921.
Impaired fetal growth is one of the most important causes of prematurity, stillbirth and infant mortality. The pathogenesis of idiopathic fetal growth restriction (FGR) is poorly understood but is thought to be multifactorial and comprise a range of genetic causes. This research aimed to investigate non-coding RNAs (lncRNAs) in the placentas of male and female fetuses affected by FGR. RNA-Seq data were analyzed to detect lncRNAs, their potential target genes and circular RNAs (circRNAs); a differential analysis was also performed. The multilevel bioinformatic analysis enabled the detection of 23,137 placental lncRNAs and 4263 of them were classified as novel. In FGR-affected female fetuses' placentas (ff-FGR), among 19 transcriptionally active regions (TARs), five differentially expressed lncRNAs (DELs) and 12 differentially expressed protein-coding genes (DEGs) were identified. Within 232 differentially expressed TARs identified in male fetuses (mf-FGR), 33 encompassed novel and 176 known lncRNAs, and 52 DEGs were upregulated, while 180 revealed decreased expression. In ff-FGR , lncRNA expression was significantly correlated with five DEGs, and in mf-FGR, 25 TARs were associated with DELs correlated with 157 unique DEGs. Backsplicing circRNA processes were detected in the range of lncRNA, in both ff- and mf-FGR placentas. The performed global lncRNAs characteristics in terms of fetal sex showed dysregulation of DELs, DEGs and circRNAs that may affect fetus growth and pregnancy outcomes. In female placentas, DELs and DEGs were associated mainly with the vasculature, while in male placentas, disturbed expression predominantly affected immune processes.
胎儿生长受限是早产、死产和婴儿死亡的最重要原因之一。特发性胎儿生长受限（FGR）的发病机制尚不清楚，但被认为是多因素的，并包含一系列遗传原因。本研究旨在研究受 FGR 影响的男性和女性胎儿胎盘中的非编码 RNA（lncRNA）。对 RNA-Seq 数据进行了分析，以检测 lncRNA、它们的潜在靶基因和环状 RNA（circRNA）；还进行了差异分析。多层次的生物信息学分析使我们能够检测到 23137 个胎盘 lncRNA，其中 4263 个被归类为新型 lncRNA。在受 FGR 影响的女性胎儿胎盘（ff-FGR）中，在 19 个转录活跃区（TARs）中，鉴定出 5 个差异表达的 lncRNA（DELs）和 12 个差异表达的蛋白质编码基因（DEGs）。在受 FGR 影响的男性胎儿（mf-FGR）中，在 232 个差异表达的 TARs 中，有 33 个包含新型和 176 个已知的 lncRNA，有 52 个上调，有 180 个下调。在 ff-FGR 中，lncRNA 的表达与 5 个 DEG 显著相关，在 mf-FGR 中，有 25 个 TARs 与 157 个独特的 DEG 相关的 DELs 相关。在 ff-FGR 和 mf-FGR 胎盘组织中均检测到 backsplicing circRNA 过程。从胎儿性别角度对 lncRNA 进行了全面的特征分析，结果表明 DELs、DEGs 和 circRNAs 的失调可能会影响胎儿的生长和妊娠结局。在女性胎盘中，DELs 和 DEGs 主要与血管系统相关，而在男性胎盘中，失调的表达主要影响免疫过程。
