Marcondes João Paulo de Castro, Andrade Pablo Felipe Bertolini, Sávio André Luiz Ventura, Silveira Maruhen Amir Datsch, Rudge Marilza Vieira Cunha, Salvadori Daisy Maria Fávero
UNESP - São Paulo State University, Medical School, Botucatu, SP, Brazil; UNESP - São Paulo State University, Bioscience Institute, Botucatu, SP, Brazil.
UNESP - São Paulo State University, Medical School, Botucatu, SP, Brazil.
Mutat Res Genet Toxicol Environ Mutagen. 2018 Dec;836(Pt B):90-96. doi: 10.1016/j.mrgentox.2018.06.009. Epub 2018 Jun 2.
Several findings suggest that in utero stressor stimuli can alter fetal development by promoting transcriptional changes, and predisposing the neonate to diseases later in life. This study aimed to investigate whether a hyperglycemic environment in pregnant women with gestational diabetes mellitus (GDM) is able to cause fetal genetic alterations and predispose neonates to obesity. Transcriptional alteration of SIRT1, TP53 and BCL2 genes, miR-181a (a SIRT1 or BCL2 regulator) and telomere length were evaluated in placental and umbilical-cord blood cells. Healthy (HP; n = 20) and GDM (n = 20) pregnant women and their respective neonates were included in the study. Additionally, obese (n = 20) and eutrophic (n = 20) adults also participated as reference populations. Gene expression data showed down-regulation of BCL2 in umbilical-cord and peripheral blood cells from GDM neonates and obese adults, respectively. The miR-181a was down-regulated only in umbilical-cord blood cells of GDM neonates. Telomere length presented no significant difference. In conclusion, our study demonstrated that the GDM hyperglycemic intrauterine environment promotes transcriptional alterations in BCL2 and miR-181a in neonate umbilical-cord blood cells. Furthermore, both GDM neonates and obese subjects share the same transcriptional alteration in BCL2. Considering the relationship between obesity development and the functions regulated by these two genes, BCL2 and miR-181a could be adopted as potential biomarkers for childhood obesity. However, further study designs are recommended to confirm this hypothesis.
多项研究结果表明，子宫内应激源刺激可通过促进转录变化来改变胎儿发育，并使新生儿在日后易患疾病。本研究旨在调查妊娠期糖尿病（GDM）孕妇的高血糖环境是否会导致胎儿基因改变并使新生儿易患肥胖症。在胎盘和脐带血细胞中评估了SIRT1、TP53和BCL2基因、miR-181a（一种SIRT1或BCL2调节剂）的转录变化以及端粒长度。该研究纳入了健康（HP；n = 20）和GDM（n = 20）孕妇及其各自的新生儿。此外，肥胖（n = 20）和营养正常（n = 20）的成年人也作为参考人群参与了研究。基因表达数据显示，GDM新生儿和肥胖成年人脐带血和外周血细胞中的BCL2分别下调。miR-181a仅在GDM新生儿的脐带血细胞中下调。端粒长度无显著差异。总之，我们的研究表明，GDM高血糖宫内环境促进了新生儿脐带血细胞中BCL2和miR-181a的转录变化。此外，GDM新生儿和肥胖受试者在BCL2方面存在相同的转录变化。考虑到肥胖症发展与这两个基因调控功能之间的关系，BCL2和miR-181a可作为儿童肥胖症的潜在生物标志物。然而，建议采用进一步的研究设计来证实这一假设。
