Department of Obstetrics and Gynecology, Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, Zhejiang, People's Republic of China.
The Affiliated Hangzhou Women's Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, People's Republic of China.
Clin Epigenetics. 2022 May 23;14(1):69. doi: 10.1186/s13148-022-01289-5.
Gestational diabetes mellitus (GDM) is a common pregnancy-specific disease and is growing at an alarming rate worldwide, which can negatively affect the health of pregnant women and fetuses. However, most studies are limited to one tissue, placenta or umbilical cord blood, usually with one omics assay. It is thus difficult to systematically reveal the molecular mechanism of GDM and the key influencing factors on pregnant women and offspring.
We recruited a group of 21 pregnant women with GDM and 20 controls without GDM. For each pregnant woman, reduced representation bisulfite sequencing and RNA-seq were performed using the placenta and paired neonatal umbilical cord blood specimens. Differentially methylated regions (DMRs) and differentially expressed genes (DEGs) were identified with body mass index as a covariate. Through the comparison of GDM and control samples, 2779 and 141 DMRs, 1442 and 488 DEGs were identified from placenta and umbilical cord blood, respectively. Functional enrichment analysis showed that the placenta methylation and expression profiles of GDM women mirrored the molecular characteristics of "type II diabetes" and "insulin resistance." Methylation-altered genes in umbilical cord blood were associated with pathways "type II diabetes" and "cholesterol metabolism." Remarkably, both DMRs and DEGs illustrated significant overlaps among placenta and umbilical cord blood samples. The overlapping DMRs were associated with "cholesterol metabolism." The top-ranking pathways enriched in the shared DEGs include "growth hormone synthesis, secretion and action" and "type II diabetes mellitus."
Our research demonstrated the epigenetic and transcriptomic alternations of GDM women and offspring. Our findings emphasized the importance of epigenetic modifications in the communication between pregnant women with GDM and offspring, and provided a reference for the prevention, control, treatment, and intervention of perinatal deleterious events of GDM and neonatal complications.
妊娠糖尿病（GDM）是一种常见的妊娠特异性疾病，在全球范围内呈惊人的增长速度，可对孕妇和胎儿的健康产生负面影响。然而，大多数研究仅限于一种组织，胎盘或脐带血，通常使用一种组学检测。因此，很难系统地揭示 GDM 的分子机制以及对孕妇和后代的关键影响因素。
我们招募了 21 名患有 GDM 的孕妇和 20 名没有 GDM 的对照者。对每位孕妇，使用胎盘和配对的新生儿脐带血标本进行了代表性降低的亚硫酸氢盐测序和 RNA-seq。通过体重指数作为协变量，鉴定了差异甲基化区域（DMR）和差异表达基因（DEG）。通过 GDM 和对照样本的比较，分别从胎盘和脐带血中鉴定出 2779 和 141 个 DMR，1442 和 488 个 DEG。功能富集分析表明，GDM 女性胎盘的甲基化和表达谱反映了“2 型糖尿病”和“胰岛素抵抗”的分子特征。脐带血中甲基化改变的基因与“2 型糖尿病”和“胆固醇代谢”途径相关。值得注意的是，胎盘和脐带血样本中的 DMR 和 DEG 均存在显著重叠。重叠的 DMR 与“胆固醇代谢”相关。在共享 DEG 中富集的前导途径包括“生长激素合成、分泌和作用”和“2 型糖尿病”。
我们的研究表明 GDM 女性及其后代存在表观遗传和转录组学改变。我们的研究结果强调了表观遗传修饰在 GDM 孕妇与后代之间的沟通中的重要性，并为 GDM 孕妇及其新生儿不良围产期事件和新生儿并发症的预防、控制、治疗和干预提供了参考。
