Department of Obstetrics, The First Affiliated Hospital of China Medical University, Shenyang, China.
Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China.
J Obstet Gynaecol. 2021 Aug;41(6):881-887. doi: 10.1080/01443615.2020.1819211. Epub 2020 Nov 24.
Maternal diabetes may lead to long-term risks for the offspring. The study aims at identifying the potential crucial genes and pathways associated with foetal metabolism and malformation of gestational diabetes mellitus (GDM). Gene Expression Series 49524 and 87295 were downloaded from Gene Expression Omnibus database, including eight from GDM and eight from non-GDM. A total of 35 differentially expressed genes were identified. Gene ontology functional annotation and signalling pathway analyses were performed. Four hub genes were identified by protein-protein interaction network: SHH, E2F1, STAT1, and HOXA9. The four hub genes were assessed by western blot and real-time quantitative PCR in clinical samples. The results of this data mining and integration help to reveal the pathophysiologic and molecular mechanism imprinted in primary umbilical cord-derived cells from GDM offspring. These genes and pathways identified are potential stratification biomarkers and provide further insight for developing therapeutic intervention for the offspring of diabetic mothers.Impact statement Maternal diabetes may lead to long-term risks for the offspring. A high glucose environment might change the umbilical cord expression of genes implicated in foetal metabolism and development. However, underlying molecular mechanisms have not been investigated thoroughly. GO functional annotation showed that the biological functions of differentially expressed genes mainly involved in metanephros development, salivary gland morphogenesis, fat cell differentiation, vasculogenesis, muscle cell proliferation, heart morphogenesis and Wnt signalling pathway. Signalling pathway analyses found that these differentially expressed genes mainly implicated in the apoptosis, cell cycle, Hedgehog, P53, and NOTCH signalling pathway. Four hub genes were identified by protein-protein interaction network: , , and . The genes and pathways identified in the present study are potential stratification biomarkers and provide further insight for developing therapeutic intervention for the offspring of diabetic mothers.
母体糖尿病可能会给后代带来长期风险。本研究旨在确定与胎儿代谢和妊娠糖尿病（GDM）畸形相关的潜在关键基因和途径。从基因表达综合数据库中下载了基因表达系列 49524 和 87295，其中包括 8 个来自 GDM 和 8 个来自非 GDM。共鉴定出 35 个差异表达基因。进行了基因本体功能注释和信号通路分析。通过蛋白质-蛋白质相互作用网络鉴定了 4 个枢纽基因：SHH、E2F1、STAT1 和 HOXA9。在临床样本中通过 Western blot 和实时定量 PCR 评估了这 4 个枢纽基因。这项数据挖掘和整合的结果有助于揭示 GDM 后代原代脐带来源细胞中印记的病理生理和分子机制。鉴定出的这些基因和途径可能是潜在的分层生物标志物，并为开发糖尿病母亲后代的治疗干预措施提供了进一步的见解。
母体糖尿病可能会给后代带来长期风险。高血糖环境可能会改变与胎儿代谢和发育相关的脐带基因表达。然而，潜在的分子机制尚未得到深入研究。GO 功能注释显示，差异表达基因的生物学功能主要涉及后肾发育、唾液腺形态发生、脂肪细胞分化、血管生成、肌肉细胞增殖、心脏形态发生和 Wnt 信号通路。信号通路分析发现，这些差异表达基因主要与细胞凋亡、细胞周期、Hedgehog、P53 和 NOTCH 信号通路有关。通过蛋白质-蛋白质相互作用网络鉴定了 4 个枢纽基因：、、和。本研究中鉴定的基因和途径可能是潜在的分层生物标志物，并为开发糖尿病母亲后代的治疗干预措施提供了进一步的见解。
