Journal of Shanghai Jiao Tong University (Medical Science) ›› 2022, Vol. 42 ›› Issue (4): 422-432.doi: 10.3969/j.issn.1674-8115.2022.04.004

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Neuropsychiatric effects of gestational diabetes mellitus in adult offspring in C57BL/6J mice

WU Xiafei1(), FANG Jie1, QI Hongbo1,2, YU Xinyang1()   

  1. 1.Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
    2.The Chongqing Health Center for Women and Children, Chongqing 400010, China
  • Received:2021-12-01 Accepted:2022-03-16 Online:2022-04-28 Published:2022-04-28
  • Contact: YU Xinyang;
  • Supported by:
    National Natural Science Foundation of China(81901507)

Abstract: Objective

·To investigate the influence of gestational diabetes mellitus (GDM) on the neuropsychiatric function of C57BL/6J adult offspring mice.


·C57BL/6J mice aged 8 weeks were randomly divided into the GDM group and the control group. GDM model was induced by a high-fat diet (HFD). Fasting glucose, oral glucose tolerance test (OGTT), and insulin tolerance test (ITT) of the pregnant mice were tested to verify whether the model was successfully induced. The offspring were fed with a standard diet for 18 weeks, and then underwent open field test (OFT), elevated plus maze (EPMT), elevated zero maze test (EZMT), forced swimming test (FST), tail suspension test (TST), and sucrose preference test (SPT) to test the emotional behaviors of the offspring mice. The hippocampus was collected after the behavioral experiments for histological verification. Hematoxylin-eosin (H-E) staining and silver staining were used to determine the structure and morphology of the offspring hippocampus of the GDM group, and immunofluorescence staining was used to detect the number of neuron marker and astrocyte marker positive cells. Real time quantitative PCR (RT-qPCR) was used to detect the expression of dopamine (DA), 5-hydroxytryptamine (5-HT), and brain-derived neural factor (BDNF), cAMP response element-binding protein (CREB) relative genes (Drd1, Htr2a, Bdnf and Creb1) in the hippocampus. One-way ANOVA was used for comparison among multiple groups, and independent-sample t-test was used to analyze differences between two groups.


·The GDM model induced by HFD in C57BL/6J mice showed that blood glucose levels and AUC were significantly increased at each time point of OGTT, and insulin tolerance was decreased, confirming that the GDM model was successfully established. The results of OFT, EPMT and EZMT in the progeny showed no statistical difference between the GDM group and the control group. The FST, TST and SPT displayed that the immobility time was observably increased, and the percentage of sucrose preference was markedly reduced in the GDM group, and the difference in F1 female mice was more significant (P=0.000). The expression of Drd1, Htr2a and Bdnf was reduced in the GDM group compared with the control group. Analysis of H-E and silver staining results showed that there was no difference in the structure of the hippocampus between the two groups, but the number of neurons and astrocytes decreased in the GDM group.


·GDM is associated with neuropsychiatric disorders in adult offspring of C57BL/6J mice, which mainly manifest as depression tendency instead of anxiety tendency.

Key words: gestational diabetes mellitus, offspring, neurological disorders, mood disorders, depressive disorders, anxiety disorders

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