Zhang Yanan, Liu Yufen, Shi Yanyan, Bai Chunyu, Wang Ting, Ruan Fang, Hu Chuanbing
Department of Obstetrics, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, 272029, PR China.
Department of Pediatric Surgery, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, 272029, PR China.
Heliyon. 2024 Jun 7;10(12):e32518. doi: 10.1016/j.heliyon.2024.e32518. eCollection 2024 Jun 30.
In recent years, there has been a notable rise in the incidence of pregnancies complicated by gestational diabetes mellitus (GDM), characterized by glucose intolerance first identified during pregnancy. Analysis of placental tissue has revealed that placentas from women with GDM tend to be larger and heavier compared to control placentas, indicating potential changes in trophoblast proliferation, differentiation, and apoptosis. In this study, transcriptome sequencing was conducted on placentas obtained from both normal pregnancies and pregnancies with GDM to investigate the molecular mechanisms underlying this condition. The original sequencing data were subjected to sequencing analysis, resulting in the identification of 935 upregulated genes and 256 downregulated genes. The KEGG and GO analysis techniques on differential genes uncovered evidence suggesting that the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway may contribute to the pathogenesis of GDM. Subsequent analysis indicated that the expression levels of matrix metalloproteinases (MMP) 11, MMP12, MMP14, and MMP15, which are regulated by the PI3K/Akt pathway, were upregulated in the placentas of patients with GDM when compared to those of individuals with normal placental function. Additionally, our investigation into alternative splicing patterns revealed an increase in exon skipping alternative splicing of CSF3R in the placenta of patients with GDM compared to that in the control group. The CSF3R-PI3K-MMP pathway is speculated to regulate the pathogenesis of GDM.
近年来，妊娠合并妊娠期糖尿病（GDM）的发病率显著上升，其特征为孕期首次发现的葡萄糖不耐受。对胎盘组织的分析显示，与对照胎盘相比，GDM患者的胎盘往往更大、更重，这表明滋养层细胞的增殖、分化和凋亡可能发生了变化。在本研究中，对正常妊娠和GDM妊娠的胎盘进行了转录组测序，以探究这种情况背后的分子机制。对原始测序数据进行测序分析后，共鉴定出935个上调基因和256个下调基因。对差异基因的KEGG和GO分析技术揭示了证据，表明磷酸肌醇3激酶（PI3K）/Akt信号通路可能与GDM的发病机制有关。随后的分析表明，受PI3K/Akt通路调控的基质金属蛋白酶（MMP）11、MMP12、MMP14和MMP15在GDM患者胎盘组织中的表达水平高于胎盘功能正常者。此外，我们对可变剪接模式的研究发现，与对照组相比，GDM患者胎盘中CSF3R的外显子跳跃可变剪接增加。推测CSF3R-PI3K-MMP通路调控GDM的发病机制。
