Mechanism of Placenta Damage in Gestational Diabetes Mellitus by Investigating TXNIP of Patient Samples and Gene Functional Research in Cell Line

Sarina,; Li, Dong Fang; Feng, Zong Qi; Du, Jie; Wen, Zhang; Huang, Na; Jia, Jian Chao; Wu, Zhou Ying; Alamusi,; Wang, Yong Yun; Ji, Xiao; Yu, Lan

doi:10.1007/s13300-019-00713-z

Cited by 27 publications

(9 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Known as a highly specialized organ during pregnancy, the placenta serves as the interface between maternal and fetal circulation (35). In recent years, the key role of the placenta in the occurrence and development of GDM has been reported by multiple studies (36)(37)(38). Currently, IR is the critical pathophysiological characteristic of GDM, which is also found during normal pregnancy.…”

Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency

Tan

et al. 2021

Exp Ther Med

View full text Add to dashboard Cite

The placenta may play a key role in the activation of inflammation and initiation of insulin resistance (IR) during gestational diabetes mellitus (GDM) pathogenesis. Interleukin (IL)-1β and IL-18, regulated by NLR family pyrin domain containing-3 (NLRP3) inflammasome, are important inflammatory cytokines in the initiation of maternal IR during GDM. However, the mechanism responsible for the regulatory of NLRP3 inflammasome in placenta remains unknown. Hydrogen sulfide (H 2 S) exerts anti-inflammatory function partially via suppressing the activation of the NLPR3 inflammasome. The present study aimed to investigate the role of NLRP3 inflammasome, H 2 S synthetase cystathionine-γ-lyase (CSE) and cystathionine-β-synthetase (CBS) in placenta in the pathogenesis of GDM. Clinical placenta samples were collected from pregnant women with GDM (n=16) and healthy pregnant women at term (n=16). Western blot analysis was performed to detect the protein expression levels of NLRP3, cleaved caspase-1, CBS and CSE in the placenta samples. Pearson's correlation analysis was performed to assess the correlation between NLRP3 inflammasome and H 2 S synthetase. Human placental cells were cultured and treated with different concentrations of NaHS (0, 10, 25 and 50 nmol/l) or L-cysteine (0, 0.25, 0.50 and 1.00 mmol/l). In addition, western blot analysis was performed to detect the protein expression levels of NLRP3 and cleaved caspase-1, while ELISA was performed to measure the production of IL-1β and IL-18 in the culture media. The results demonstrated that the expression levels of NLRP3 and cleaved caspase-1 increased, while the expression levels of CBS and CSE decreased in the placenta samples. In addition, the expression levels of NLRP3 and cleaved caspase-1 were inversely correlated with the expression levels of CBS and CSE. Notably, NaHS and L-cysteine significantly suppressed the expression levels of NLRP3 and cleaved caspase-1, and the production of IL-1 and IL-18 in human placental cells. Taken together, the results of the present study suggest that H 2 S synthetase deficiency in placenta may contribute to excessive activation of NLRP3 inflammasome in GDM.

show abstract

Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency

Tan

et al. 2021

Exp Ther Med

View full text Add to dashboard Cite

show abstract

“…Physiological oxidative stress is indeed a protective and adaptive mechanism of the body during normal pregnancies. However, excessive active oxygen can disrupt the balance between oxidation and antioxidation, cause pathological oxidative stress, and ultimately lead to tissue damage in GDM[ 6 , 19 ]. A previous study showed that placental cell biology and mitochondrial dysfunction are central to the pathophysiology of many gestational diseases, such as GDM, preeclampsia, preterm birth, and fetal growth restriction[ 20 ].…”

Section: Discussionmentioning

confidence: 99%

p66Shc-mediated oxidative stress is involved in gestational diabetes mellitus

Huang¹,

Sun²,

Liu³

et al. 2021

WJD

View full text Add to dashboard Cite

BACKGROUND Gestational diabetes mellitus (GDM) is associated with a heightened level of oxidative stress, which is characterized by the overproduction of reactive oxygen species (ROS) from mitochondria. Previous studies showed that mitochondrial dysfunction is regulated by dynamin-related protein 1 (Drp1) and p66Shc in GDM. AIM The aim was to investigate the expression of Drp1 and p66Shc and their possible mechanisms in the pathogenesis of GDM. METHODS A total of 30 pregnant women, 15 with GDM and 15 without GDM, were enrolled. Peripheral blood mononuclear cells and placental tissue were collected. The human JEG3 trophoblast cell line was cultivated in 5.5 mmol/L or 30 mmol/L glucose and transfected with wild-type (wt)-p66Shc and p66Shc siRNA. P66Shc and Drp1 mRNA levels were detected by quantitative real-time polymerase chain reaction. The expression of p66Shc and Drp1 was assayed by immunohistochemistry and western blotting. ROS was assayed by dihydroethidium staining. RESULTS The p66Shc mRNA level was increased in the serum ( P < 0.01) and placentas ( P < 0.01) of women with GDM, and the expression of Drp1 mRNA and protein were also increased in placentas ( P < 0.05). In JEG3 cells treated with 30 mmol/L glucose, the mRNA and protein expression of p66Shc and Drp1 were increased at 24 h (both P < 0.05), 48 h (both P < 0.01) and 72 h (both P < 0.001). ROS expression was also increased. High levels of Drp1 and ROS expression were detected in JEG3 cells transfected with wt-p66Shc ( P < 0.01), and low levels were detected in JEG3 cells transfected with p66Shc siRNA ( P < 0.05). CONCLUSION The upregulated expression of Drp1 and p66shc may contribute to the occurrence and development of GDM. Regulation of the mitochondrial fusion-fission balance could be a novel strategy for GDM treatment.

show abstract

“…The rate of glucose flux to the fetus is controlled by the maternal-to-fetal glucose concentration gradient across the placenta ( 33 ). Hyperglycemia-induced apoptosis of non-proliferative syncytiotrophoblast cells leaves incomplete holes in the placenta, which will cause a large flux of glucose into the fetal blood circulation ( 34 ). Data have demonstrated that women with higher FPG levels at baseline had a greater risk of developing GDM at approximately 26 weeks, which coincides with the period of elevated maternal endogenous glucose production and reduced insulin sensitivity ( 35 , 36 ).…”

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

View full text Add to dashboard Cite

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.

show abstract

Mechanism of Placenta Damage in Gestational Diabetes Mellitus by Investigating TXNIP of Patient Samples and Gene Functional Research in Cell Line

Cited by 27 publications

References 73 publications

NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency

NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency

p66Shc-mediated oxidative stress is involved in gestational diabetes mellitus

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

Contact Info

Product

Resources

About