High glucose condition inhibits trophoblast proliferation, migration and invasion by downregulating placental growth factor expression

Tao, Jun; Xia, Lin-Zhen; Chen, Jiaojiao; Zeng, Jie; Meng, Jun; Wu, Shiyuan; Zuo, Wang

doi:10.1111/jog.14341

Cited by 10 publications

(6 citation statements)

References 65 publications

(76 reference statements)

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“…Here, we showed in vitro an upregulation of trophoblast invasion by hyperglycemia in the first trimester of pregnancy. Although high glucose inhibits cell migration and invasion in HTR-8/SVNeo cells [39,40], we have previously shown that placental matrix metalloproteinase 14, an extracellular matrix-degrading protease crucial for trophoblast invasion, is upregulated by T1DM in early pregnancy [17]. This highlights the importance of using first trimester placental tissue and primary trophoblasts, since results in cell lines do not always reflect the in vivo situation.…”

Section: Discussionmentioning

confidence: 96%

Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion

Majali‐Martinez

Weiss-Fuchs

Miedl

et al. 2021

IJMS

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Type 1 diabetes mellitus (T1DM) is associated with reduced fetal growth in early pregnancy, but a contributing role of the placenta has remained elusive. Thus, we investigated whether T1DM alters placental development in the first trimester. Using a protein array, the level of 60 cell-cycle-related proteins was determined in human first trimester placental tissue (gestational week 5–11) from control (n = 11) and T1DM pregnancies (n = 12). Primary trophoblasts (gestational week 7–12, n = 32) were incubated in the absence (control) or presence of hyperglycemia (25 mM D-glucose) and hyperosmolarity (5.5 mM D-glucose + 19.5 mM D-mannitol). We quantified the number of viable and dead trophoblasts (CASY Counter) and assessed cell cycle distribution (FACS) and trophoblast invasion using a transwell assay. T1DM was associated with a significant (p < 0.05) downregulation of Ki67 (−26%), chk1 (−25%), and p73 (−26%). The number of viable trophoblasts was reduced under hyperglycemia (−23%) and hyperosmolarity (−18%), whereas trophoblast invasion was increased only under hyperglycemia (+6%). Trophoblast cell death and cell cycle distribution remained unaffected. Collectively, our data demonstrate that hyperglycemia decreases trophoblast proliferation as a potential contributing factor to the reduced placental growth in T1DM in vivo.

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Section: Discussionmentioning

confidence: 96%

Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion

Majali‐Martinez

Weiss-Fuchs

Miedl

et al. 2021

IJMS

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“…Recently, many circRNAs have been identified as potential diagnostic markers for GDM with notable function in the regulation of trophoblast cell biological functions (Chen et al, 2021;Wang et al, 2020). In addition, existing research unveiled that HG treatment inhibited viability, migration, and invasion of HTR-8/SVneo cells (Tao et al, 2020). In the current study, HTR-8/SVneo cells were treated with 25 mM glucose to mimic damaged trophoblast cell in GDM, and then we illustrated that circSESN2 promoted the inflammation and apoptosis of HG-treated HTR-8/SVneo cells by regulating IGF2BP2 protein expression, thereby increasing HG-induced loss of invasion and migration.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA SESN2 aggravates gestational trophoblast cell damage induced by high glucose by binding to IGF2BP2

Huang

Guo

2023

Molecular Reproduction Devel

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Gestational diabetes mellitus (GDM) is a common disease in pregnant women that threatens maternal and fetal health. Circular RNAs (circRNAs) have been considered potential diagnostic markers for GDM and affect trophoblast cell phenotypes. This study aimed to explore the effect of circSESN2 on high glucose (HG)-treated trophoblast cells. Peripheral blood and placental tissues were taken from patients with GDM, in which circSESN2 and IGF2BP2 levels were detected by quantitative reverse transcription polymerase chain reaction and/or western blot. HTR-8/SVneo cells were treated with 25 mM glucose and transduced with circSESN2 or IGF2BP2 knockdown vectors. HTR-8/SVneo cell viability was evaluated by MTT assay, cell migration by scratch test, and cell invasion by transwell assay, IL-1β, IL-6, TNF-α, malondialdehyde, and superoxide dismutase levels by ELISA or kits, and reactive oxygen species levels by DCFH-DA probes. The binding between circSESN2 and IGF2BP2 was verified by RNA pulldown and RIP assays. CircSESN2 and IGF2BP2 were overexpressed in GDM patients. Suppressing circSESN2 or IGF2BP2 increased HTR-8/SVneo cell invasion and migration, decreased cell apoptosis, and reduced pro-inflammatory cytokine release and oxidative stress injury. CircSESN2 bound IGF2BP2 and IGF2BP2 overexpression accelerated HG-induced HTR-8/SVneo cell damage despite circSESN2 knockdown. Collectively, circSESN2 exacerbated HG-induced trophoblast cell damage by binding IGF2BP2 and upregulating its protein expression.

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“…The underlying biological mechanisms may be attributed to a combination of glucosemediated effects mediated by mitochondrial function, epigenetic modification, and oxidative stress (25)(26)(27)(28). Experimental data have indicated that trophoblast cell exposure to hyperglycemia limits migration and invasion, often with dose-response patterns, which further impedes the normal function of the placental villi and interferes with the placentation process (29). These findings suggest that decreased fetal growth may be associated with the worsening of FPG within the respective normal reference range.…”

Section: Discussionmentioning

confidence: 99%

Observations of the Effects of Maternal Fasting Plasma Glucose Changes in Early Pregnancy on Fetal Growth Profiles and Birth Outcomes

et al. 2021

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IntroductionAlthough the role of maternal hyperglycemia on birth outcomes is clear, literature regarding fetal growth is scarce. We examined the possible associations between maternal fasting plasma glucose (FPG) and fetal growth.Materials and MethodsA total of 35,981 singleton-pregnant women with FPG in the first trimester were included. Fetal growth parameters were measured during pregnancy by ultrasound at mid and late pregnancy. Information on birth characteristics was retrieved from medical records. We used multivariable linear and logistic regression to determine the associations between FPG and z-scores of fetal parameters and risks of birth outcomes and to assess effect modification by maternal characteristics.ResultsA per-unit increase in FPG levels was negatively associated with fetal parameters in mid pregnancy but positively correlated with those in late pregnancy and with birth characteristics. The effect estimates in late pregnancy were attenuated by maternal pre-pregnancy body mass index (BMI). A significant relationship between FPG and abdominal circumference (AC), an indicator of fetal adiposity, was sustained in subgroups of women with advanced age, positive family history of diabetes, and multiparity in fully adjusted models. After stratification by BMI, high FPG was associated with accelerated AC only in normal controls (0.044 SD; 95% CI: 0.010, 0.079) and overweight/obese women (0.069 SD; 95% CI: -0.002, 0.140) but not in underweight women. High FPG was an independent risk factor for large-for-gestational age in the whole group and stratified subgroups.ConclusionsIncreased FPG in early pregnancy is closely related to fetal growth. Maternal characteristics may modify the associations between FPG and fetal adiposity in late pregnancy.

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High glucose condition inhibits trophoblast proliferation, migration and invasion by downregulating placental growth factor expression

Cited by 10 publications

References 65 publications

Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion

Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion

Circular RNA SESN2 aggravates gestational trophoblast cell damage induced by high glucose by binding to IGF2BP2

Observations of the Effects of Maternal Fasting Plasma Glucose Changes in Early Pregnancy on Fetal Growth Profiles and Birth Outcomes

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