Alterations of transcriptome expression, cell cycle, and mitochondrial superoxide reveal foetal endothelial dysfunction in Saudi women with gestational diabetes mellitus

Samar Sultan; Farid Ahmed; Osama Bajouh; Hans-Juergen Schulten; Nadia Bagatian; Roaa Al-Dayini; Ohoud Subhi; Sajjad Karim; Sultanah Almalki

doi:10.1507/endocrj.EJ21-0189

ORIGINAL

Alterations of transcriptome expression, cell cycle, and mitochondrial superoxide reveal foetal endothelial dysfunction in Saudi women with gestational diabetes mellitus

Samar Sultan, Farid Ahmed, Osama Bajouh, Hans-Juergen Schulten, Nadia Bagatian, Roaa Al-Dayini, Ohoud Subhi, Sajjad Karim, Sultanah Almalki

Author information

Samar Sultan
https://orcid.org/0000-0003-1194-8545
Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
Farid Ahmed
Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
Osama Bajouh
Department of Obstetrics and Gynaecology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
Centre of Innovation in Personalized Medicine, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
Hans-Juergen Schulten
Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
Nadia Bagatian
Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
Roaa Al-Dayini
Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
Ohoud Subhi
Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
Sajjad Karim
Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
Sultanah Almalki
Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia

Keywords: Endothelial dysfunction, Mitochondrial superoxide, Cell cycle, Gestational diabetes, Transcriptome profile

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Supplementary material

2021 Volume 68 Issue 9 Pages 1067-1079

DOI https://doi.org/10.1507/endocrj.EJ21-0189

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Abstract

Gestational diabetes mellitus (GDM) affects one in four Saudi women and is associated with high risks of cardiovascular diseases in both the mother and foetus. It is believed that endothelial cells (ECs) dysfunction initiates these diabetic complications. In this study, differences in the transcriptome profiles, cell cycle distribution, and mitochondrial superoxide (MTS) between human umbilical vein endothelial cells (HUVECs) from GDM patients and those from healthy (control) subjects were analysed. Transcriptome profiles were generated using high-density expression microarray. The selected four altered genes were validated using qRT-PCR. MTS and cell cycle were analysed by flow cytometry. A total of 84 altered genes were identified, comprising 52 upregulated and 32 downregulated genes in GDM.HUVECs. Our selection of the four interested altered genes (TGFB2, KITLG, NEK7, and IGFBP5) was based on the functional network analysis, which revealed that these altered genes are belonging to the highest enrichment score associated with cellular function and proliferation; all of which may contribute to ECs dysfunction. The cell cycle revealed an increased percentage of cells in the G2/M phase in GDM.HUVECs, indicating cell cycle arrest. In addition, we found that GDM.HUVECs had increased MTS generation. In conclusion, GDM induces persistent impairment of the biological functions of foetal ECs, as evidenced by analyses of transcriptome profiles, cell cycle, and MTS even after ECs culture in vitro for several passages under normal glucose conditions.

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