Abstract:SUMMARY: Placental angiogenesis, is essential for embryonic and fetal development. In this study, 18 gestational diabetes mellitus and 22 control pregnancies were included. Gestational diabetes mellitus (GDM) groups compared to the control group significantly higher values were detected (p<0.01). The following histological results were assessed; villous immaturity, chorangiosis, presence of, sncytial knots,mononuclear cell infiltration ischemia and fibrinoid necrosis. To evaluate and compare the placental hist… Show more
“…Although it would be sensible to assume the involvement of GDM-CMSCs in hypervascularisation, CMSCs derived from GDM placenta did not show an increase in vasculogenesis-associated gene expression or angiogenesis pathway activity, suggesting that CMSCs may not contribute to placental hypervascularisation in GDM. On the contrary, immunohistochemistry staining of increased VEGF protein in cytotrophoblast and syncytiotrophoblast cells of GDM chronic villi [38,39], flow cytometry identifying elevated levels of VEGF receptors on endothelial progenitor cells from GDM women [40], and increased cytokine production from Hofbauer and placental cells [41] were all associated with enhanced angiogenesis and vasculogenesis in GDM. Various cell types in GDM placenta contribute to hypervascularisation while reduced angiogenic ability in GDM-CMSCs might represent a compensatory response to counteract dysregulated angiogenesis and vascularisation or be implicated in vascular function defects of GDM placenta.…”
Background: Gestational diabetes (GDM) is a common complication of pregnancy. The impact of pregnancy complications on placental function suggests that extraembryonic stem cells in the placenta may also be affected during pregnancy. Neonatal tissue-derived stem cells, with the advantages of their differentiation capacity and noninvasive isolation processes, have been proposed as a promising therapeutic avenue for GDM management through potential cell therapy approaches. However, the influence of GDM on autologous stem cells remains unclear. Thus, studies that provide comprehensive understanding of stem cells isolated from women with GDM are essential to guide future clinical applications. Methods: Human chorionic membrane-derived stem cells (CMSCs) were isolated from placentas of healthy and GDM pregnancies. Transcriptional profiling was performed by DNA microarray, and differentially regulated genes between GDM-and Healthy-CMSCs were used to analyse molecular functions, differentiation, and pathway enrichment. Altered genes and biological functions were validated via real-time PCR and in vitro assays. Results: GDM-CMSCs displayed, vs. Healthy-CMSCs, 162 upregulated genes associated with increased migration ability, epithelial development, and growth factor-associated signal transduction while the 269 downregulated genes were strongly linked to angiogenesis and cellular metabolic processes. Notably, significantly reduced expression of detoxification enzymes belonging to the aldehyde dehydrogenase gene families (ALDH1A1/1A2, ALDH2, ALDH3) accounted for downregulation across several metabolic pathways. ALDH activity and inhibitor assays indicated that reduced gene expression of ALDHs affected ALDH enzymatic functions and resulted in oxidative stress dysregulation in GDM-CMSCs. Conclusion: Our combined transcriptional analysis and in vitro functional characterisation have provided novel insights into fundamental biological differences in GDM-and Healthy-CMSCs. Enhanced mobility of GDM-CMSCs may promote MSC migration toward injured sites; however, impaired cellular metabolic activity may negatively affect any perceived benefit.
“…Although it would be sensible to assume the involvement of GDM-CMSCs in hypervascularisation, CMSCs derived from GDM placenta did not show an increase in vasculogenesis-associated gene expression or angiogenesis pathway activity, suggesting that CMSCs may not contribute to placental hypervascularisation in GDM. On the contrary, immunohistochemistry staining of increased VEGF protein in cytotrophoblast and syncytiotrophoblast cells of GDM chronic villi [38,39], flow cytometry identifying elevated levels of VEGF receptors on endothelial progenitor cells from GDM women [40], and increased cytokine production from Hofbauer and placental cells [41] were all associated with enhanced angiogenesis and vasculogenesis in GDM. Various cell types in GDM placenta contribute to hypervascularisation while reduced angiogenic ability in GDM-CMSCs might represent a compensatory response to counteract dysregulated angiogenesis and vascularisation or be implicated in vascular function defects of GDM placenta.…”
Background: Gestational diabetes (GDM) is a common complication of pregnancy. The impact of pregnancy complications on placental function suggests that extraembryonic stem cells in the placenta may also be affected during pregnancy. Neonatal tissue-derived stem cells, with the advantages of their differentiation capacity and noninvasive isolation processes, have been proposed as a promising therapeutic avenue for GDM management through potential cell therapy approaches. However, the influence of GDM on autologous stem cells remains unclear. Thus, studies that provide comprehensive understanding of stem cells isolated from women with GDM are essential to guide future clinical applications. Methods: Human chorionic membrane-derived stem cells (CMSCs) were isolated from placentas of healthy and GDM pregnancies. Transcriptional profiling was performed by DNA microarray, and differentially regulated genes between GDM-and Healthy-CMSCs were used to analyse molecular functions, differentiation, and pathway enrichment. Altered genes and biological functions were validated via real-time PCR and in vitro assays. Results: GDM-CMSCs displayed, vs. Healthy-CMSCs, 162 upregulated genes associated with increased migration ability, epithelial development, and growth factor-associated signal transduction while the 269 downregulated genes were strongly linked to angiogenesis and cellular metabolic processes. Notably, significantly reduced expression of detoxification enzymes belonging to the aldehyde dehydrogenase gene families (ALDH1A1/1A2, ALDH2, ALDH3) accounted for downregulation across several metabolic pathways. ALDH activity and inhibitor assays indicated that reduced gene expression of ALDHs affected ALDH enzymatic functions and resulted in oxidative stress dysregulation in GDM-CMSCs. Conclusion: Our combined transcriptional analysis and in vitro functional characterisation have provided novel insights into fundamental biological differences in GDM-and Healthy-CMSCs. Enhanced mobility of GDM-CMSCs may promote MSC migration toward injured sites; however, impaired cellular metabolic activity may negatively affect any perceived benefit.
“…They did not find any mitotic activity of the Hofbauer cells, because the Ki-67 marker for cellular multiplication was negative in all the specimens examined. Yavuz et al (2015) studied VEGF and CD68 expression immunohistochemically in the placenta of mothers with GDM. They verified that the expression of VEGF and its receptors increased in the placental chorionic villi mainly in GDM, whereas in the nondiabetic villi a weak VEGF expression was detected.…”
Morphological features of the human placenta and its free chorionic villi in normal pregnancies and those with diabetes and high blood pressure. literature review.
“…78 Studies reported that hyperglycaemia, hyperinsulinaemia, dyslipidaemia and hypoxic uterine environment are the causes of VEGF and fibroblast growth factor 2 overexpression. 75,[79][80][81] When VEGF binds to its receptor, it induces the self-phosphorylation of cadherin, which causes interruptions in the adherens junctions of endothelial cells, leading to increased vascular permeability. 81,82 Although data on angiogenic factors in GDM are limited, there are recent studies suggesting that VEGF overexpression would be secondary to an increase in the angiogenic placental growth factor, which increases cell sensitivity to VEGF.…”
During pregnancy, women undergo several metabolic changes to guarantee an adequate supply of glucose to the foetus. These metabolic modifications develop what is known as physiological insulin resistance. When this process is altered, however, gestational diabetes mellitus (GDM) occurs. GDM is a multifactorial disease, and genetic and environmental factors play a crucial role in its aetiopathogenesis. GDM has been linked to both macroscopic and molecular alterations in placental tissues that affect placental physiology. This review summarizes the role of the placenta in the development of GDM from a molecular perspective, including hormonal and pro-inflammatory changes. Inflammation and hormonal imbalance, the characteristics dominating the GDM microenvironment, are responsible for placental changes in size and vascularity, leading to dysregulation in maternal and foetal circulations and to complications in the newborn. In conclusion, since the hormonal mechanisms operating in GDM have not been fully elucidated, more research should be done to improve the quality of life of patients with GDM and their future children.
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