scholarly journals miR-377 inhibition enhances the survival of trophoblast cells via upregulation of FNDC5 in gestational diabetes mellitus

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 464-471
Author(s):  
Zhaozhao Hua ◽  
Dana Li ◽  
Anqin Wu ◽  
Ting Cao ◽  
Shi Luo

Abstract Gestational diabetes mellitus (GDM) is a metabolic dysregulation closely related to both obesity and type 2 diabetes; however, the molecular mechanism underlying GDM is still unclear. The purpose of this study was to investigate the effects of microRNA-377 (miR-377-3p) and fibronectin type III domain containing 5 (FNDC5) in regulating the cell growth of trophoblasts under high glucose (HG) conditions during the development of GDM. Serum miR-377-3p was upregulated and positively correlated with fasting blood glucose level in GDM patients. miR-377-3p downregulation increased the cell vitality and suppressed the cell apoptosis of HG-treated HTR-8/SVneo and BeWo cells. Using TargetScan prediction, luciferase assay, and western blot, it was found that miR-377-3p could target FNDC5 and suppress its expression. However, FNDC5 downregulation abolished the effect of miR-377-3p inhibitor in HTR-8/SVneo cells. Together, miR-377 is a potential target for GDM biomarker, which promotes cell growth and suppresses cell apoptosis, partly through the upregulation of FNDC5.

Author(s):  
Jie Wen ◽  
Xiaoxia Bai

Gestational diabetes mellitus (GDM) is a type of diabetes that occurs during pregnancy due to abnormal maternal glucose metabolism. This study aimed to investigate the effect of miR-520h and its potential target gene on the progression of GDM. The blood samples were taken from healthy pregnant women and GDM patients. Human villous trophoblasts HTR-8/SVNEO cells were treated with 25 mM glucose and were considered as the GDM cell model. The miR-520h level was detected using qRT-PCR in the serum and GDM cell model. The correlation analysis between fasting blood-glucose (FBG) level and miR-520h expression was analyzed. The target relationship between miR-520h and mTOR was verified using dual luciferase reporter assay. HG-induced cells were transfected with miR-520h mimic or miR-520h inhibitor and pCDNA3-mTOR vector or their NCs. Cell viability, apoptosis and mTOR expression level were detected using CCK-8, flow cytometry and western blotting, respectively. The results showed that the miR-520h serum level was up-regulated in the GDM patients’ serum and GDM cell model, and was positively correlated with FBG of GDM patients. High glucose (HG) inhibited HTR-8/SVNEO cell viability and decreased mTOR expression, while it promoted apoptosis. Then, the effects of HG on HTR-8/SVNEO cells were reversed by miR-520h inhibitor. Moreover, mTOR was identified as a target gene downstream of miR-520h. The overexpression of mTOR alleviated miR-520h mimic-induced reduction in cell viability and enhancement in cell apoptosis in the GDM cell model. In conclusion, miR-520h could inhibit cell viability and promote cell apoptosis by regulating mTOR expression in the GDM cell model. Hence, miR-520h might be a potential and important marker for the diagnosis and treatment of GDM.


2012 ◽  
Vol 19 (04) ◽  
pp. 462-468
Author(s):  
M. IKRAM ◽  
SYED HAIDER HASAN ALAM ◽  
SHAFQAT MUKHTAR ◽  
M. Saeed

Introduction: Gestational diabetes mellitus is common disorder in pregnancy. It is associated with adverse pregnancy outcome. There is no consensus regarding the optimal approach to screening of gestational diabetes mellitus. The present study has tried toobserve the value of fasting blood glucose in screening of gestational diabetes. Objective: To determine the frequency of patients in whomfasting blood glucose and 100gm glucose tolerance show agreement for screening of gestational diabetes mellitus at 24 -28 wks. Studydesign: Comparative cross sectional study. Settings: The study was conducted at Gynecology and Obstetrics department Shaikh ZayedFederal Post Graduate Institute Lahore. Duration of study with dates: 6 months from 12Nov 2010 to 11 May 2011. Material and method: Thestudy included 135 booked patients with positive family history of diabetes mellitus. All patients underwent fasting blood glucose at 24-28 weeksof gestation, regardless of results of fasting blood glucose on next visit they underwent 100g oral glucose tolerance test (OGTT). The agreementbetween fasting blood glucose and 100g oral glucose tolerance test was calculated in frequency and percentages. Results: The mean age ofwomen in studied population was 27.15±3.70.Out of 135 patients 86.7 %( 117) showed agreement between results of fasting blood glucose and100g OGTT while 13.31 %( 18) showed no agreement between both of the tests. Conclusions: Fasting blood glucose is a good screeningoption for gestational diabetes mellitus along with positive history. It provides a simple, cheap and more practical test for screening of gestationaldiabetes mellitus. However diagnostic confirmation with 100g OGTT should be done.


Endocrinology ◽  
2014 ◽  
Vol 155 (5) ◽  
pp. 1982-1990 ◽  
Author(s):  
Zhonghua Shi ◽  
Chun Zhao ◽  
Xirong Guo ◽  
Hongjuan Ding ◽  
Yugui Cui ◽  
...  

Omental adipose tissue plays a central role in insulin resistance in gestational diabetes mellitus (GDM), and the molecular mechanisms leading to GDM remains vague. Evidence demonstrates that maternal hormones, such as estradiol, contribute to insulin resistance in GDM. In this study we determined the differential expression patterns of microRNAs (miRNAs) in omental adipose tissues from GDM patients and pregnant women with normal glucose tolerance using AFFX miRNA expression chips. MiR-222, 1 of 17 identified differentially expressed miRNAs, was found to be significantly up-regulated in GDM by quantitative real-time PCR (P < .01), and its expression was closely related with serum estradiol level (P < .05). Furthermore, miR-222 expression was significantly increased in 3T3-L1 adipocytes with a high concentration of 17β-estradiol stimulation (P < .01), whereas the expressions of estrogen receptor (ER)-α protein and insulin-sensitive membrane transporter glucose transporter 4 (GLUT4) protein (P < .01) were markedly reduced. In addition, ERα was shown to be a direct target of miR-222 in 3T3-L1 adipocytes by using the luciferase assay. Finally, antisense oligonucleotides of miR-222 transfection was used to silence miR-222 in 3T3-L1 adipocytes. The results showed that the expressions of ERα and GLUT4, the insulin-stimulated translocation of GLUT4 from the cytoplasm to the cell membrane and glucose uptake in mature adipocytes were dramatically increased (P < .01). In conclusion, miR-222 is a potential regulator of ERα expression in estrogen-induced insulin resistance in GDM and might be a candidate biomarker and therapeutic target for GDM.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Xuegui Zhou ◽  
Cuiping Xiang ◽  
Xiaoxia Zheng

Abstract Background Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes. Strategies that improve trophoblast cell function are important methods for GDM treatment. This study aimed to investigate the expression and diagnostic potential of microRNA-132 (miR-132) in GDM patients, and further analyzed the effects of miR-132 on HTR-8/SVneo cell proliferation. Methods Quantitative real-time PCR was applied to estimate the expression of miR-132. A receiver operating characteristics curve (ROC) analysis was performed to evaluate the diagnostic value of serum miR-132 in GDM patients. In vitro regulation of miR-132 in trophoblast cell HTR-8/SVneo was achieved by cell transfection, and the effects of miR-132 on cell proliferation were assessed using CCK-8 assay. Results Expression of miR-132 was decreased in serum and placenta tissues in GDM patients compared with the healthy women. A negative correlation was found between the serum miR-132 levels and fasting blood glucose of the GDM patients. A ROC curve shown the serum miR-132 had considerable diagnostic accuracy with an area under the curve (AUC) of 0.898. High glucose (HG) treatment induced an inhibition in HTR-8/SVneo cell proliferation and the expression of miR-132. The overexpression of miR-132 in HTR-8/SVneo cells could markedly rescued the HG - induced suppressed cell proliferation. Conclusion All the data of this study revealed the reduced expression of miR-132 in serum and placenta tissues of GDM, and serum miR-132 serves a candidate biomarker in the diagnosis of GDM. miR-132 may act a protective role against GDM via enhancing the trophoblast cell proliferation.


2021 ◽  
pp. 787-792
Author(s):  
Zainab k. Hussain ◽  
Jabbar H. Yenzeel ◽  
Hayfa H. Hassani

To study the genetic effect of gestational diabetes mellitus by study IRS1gene expression in female with Gestational diabetes mellitus. It is characterized high level of blood glucose, especially during first trimester then increased during the 2nd and 3rd trimester of the pregnancy period. The blood samples taken from one hundred twenty healthy women and female with gestational diabetes mellitus in 3rd trimester period of pregnancy, level of fasting blood glucose (FBG) also HbA1c% measured to diagnose GDM, in addition to lipid profile (cholesterol, triglyceride, HDL, LDL, and VLDL), molecular study consist of RNA extraction and qRT- PCR for IRS1gene expression determination. The fasting blood glucose mg/dl and HbA1c% level was increased highly significantly (P<0.01) between patients and control (healthy women) in 3rd trimester stage in addition lipid profile included )serum cholesterol, serum triglyceride, LDL and VLDL( (mg/dl) but level of HDL (mg/dl) was decreased highly significantly (P<0.01) between patients and control. The result showed high significant of IRS1 expression gene in control (1.00 ± 0.00) while in patients (0.147 ± 0.02). The low expression of IRS1 gene was connected with gestational diabetes mellitus comparison in control (healthy women) in Iraqi female in third trimester of pregnancy


2021 ◽  
Vol 2 (2) ◽  
pp. 58-63
Author(s):  
Aasia Kanwal ◽  
Asma Salam ◽  
Aisha Bashir

Background: Gestational diabetes mellitus leads to adverse pregnancy outcomes. Objectives: The objective of the study was to explore the relationship of spontaneous abortions with gestational diabetes mellitus in pregnant women from rural and urban Lahore. Methods: This cross-sectional study was conducted at University of Health Sciences, Lahore in 2019. Among 60 pregnant women sampled, 30 had gestational diabetes mellitus (GDM) and 30 were normal pregnant controls. Pregnant women were sampled from different hospitals of rural and urban areas of Lahore. Independent sample t-test was applied for analyzing the data. Chi- square test was used to analyze the categorical variables. Association of fasting blood glucose (FBG) and abortions was checked. Odd ratio and relative risk were calculated. Results: Mean fasting blood sugar levels were significantly higher in GDM group (105 mg/dL) as compared to non-GDM group (80.50 mg/dL) at p<0.001. The proportions of the women with increased number of abortions had significantly higher blood glucose levels (OR 5.091, 95% CI, RR 1.27). Conclusions: Gestational diabetes mellitus is associated with an increased risk of spontaneous abortions.


Author(s):  
Dr. Bipul Prasad Deka ◽  
Dr. Dimpy Begum

Gestational diabetes mellitus (GDM) is defined as glucose intolerance of variable degrees with an onset, or first recognized, during pregnancy. About 15-45% of babies born to diabetic mothers can have macrosomia. This prospective case control study was conducted in the department of Obstetrics and Gynaecology of Gauhati medical college and hospital, Guwahati, Assam during the period of 2013-2015. A total of 160 patients were included in the study. 100 patients without any glucose abnormality were taken as control and 60 patients with gestational diabetes mellitus were included in the study as cases. In this study it was found that mean birth weight in GDM cases is more than normoglycemic control. The overweight and obesity group (BMI>25) have maximum birth weight. In this study it was found that the fasting blood glucose level is maximum in mothers with baby birth weight >3.5 kg.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Qian Li ◽  
Xi Chen ◽  
Xiaoyi Wang ◽  
Qin Gao ◽  
Li Huang ◽  
...  

Abstract Objectives Studies investigating association between manganese (Mn) and type 2 diabetes (T2D) were controverial and relationship between Mn and gestational diabetes mellitus (GDM) remains unclear. We aimed to explore the association between urinary Mn levels and GDM. Methods The study population included 2093 singleton pregnant women from Tongji Maternal and Child Health Cohort (TMCHC), a prospective cohort study in China. The maternal urine specimens were collected before 20 weeks of gestation and determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Odds ratios (ORs) for GDM were compared according to urinary Mn levels in quartiles using logistic regression after adjusting for potential covariates. Stratified analyses and interactive analyses were conducted. Then restricted cubic spline (RCS) regression was applied. Association between urinary Mn levels and glucose levels was assessed by linear regression. Results The medians (interquartile range) (IQR) of urinary gestation and Mn levels were 13.2 (12.2, 15.8) weeks and 0.8 (0.4–1.4) μg/g creatinine (Cr), respectively. A total of 241 (11.5%) participants were diagnosed with GDM. The odds ratios (ORs) and 95% confidence intervals (CIs) of GDM were 1.76 (1.15, 2.71) for the third quartile of urinary Mn levels and 2.00 (1.29, 3.10) for the highest quartile compared with the lowest quartile after adjustment. The adverse effect remained in all the subgroups stratified by age, primigravida, pre-pregnancy BMI, fetal sex, family history of diabetes, BMI at OGTT and physical activity. In RCS, the adverse association was consistently showed. Higher urinary Mn levels were found to be associated with higher fasting blood glucose (FBG) (Ptrend = 0.002) but not post-prandial. Conclusions Our findings suggested a positive association between urinary Mn levels and GDM. Funding Sources This study is supported by the National Program on Basic Research Project of China and the Fundamental Research Funds for the Central Universities. Supporting Tables, Images and/or Graphs


Author(s):  
Jeyamani Baskaran ◽  
Subha Sivagami Sengodan ◽  
Anbarasi Pandian

Background: Gestational diabetes mellitus is defined as carbohydrate intolerance with its onset or first recognition during present pregnancy. Objective of present study was to compare screening accuracy of ADA and WHO criteria for screening of gestational DM.Methods: This is a prospective comparative study using ADA and WHO criteria for the screening of GDM. Our objective was to study the implication of implementing the ADA guidelines and WHO guidelines for screening and diagnosis of GDM in 200 antenatal patients at Government Mohankumaramangalam Medical College, Salem during a period of one year from July 2015 to June 2016. All antenatal women attending AN OP between 24-28 weeks of gestation are subjected to fasting blood glucose measurement followed by an oral OGTT using 75 gms of glucose load. Venous blood samples are collected at the end of 1hr and 2hr. The ADA and WHO criteria were applied separately for each subject to diagnose GDMResults: As per ADA criteria presence of any one of either, Fasting blood sugar- 92 mg (5.1 mmol/L),1 hour postprandial-180mg (10.00mmol/L), 2 hour postprandial: 153 mg (8.5 mmol/L) was used for the diagnosis of GDM.As per WHO criteria presence of any one of either, Fasting blood sugar- 126mg/dl (7 mmol/dl) or 2 hour postprandial- 140 mg/dl (7.8 mmol/dl) for diagnosis of GDM. The 2hr value has the statistical significance in the diagnosis of GDM. The 1hr value done in ADA criteria does not have statistical significance when compared to 2hr value.Conclusions: Universal screening for GDM is necessary to diagnose Gestational Diabetes Mellitus. Universal screening may not be feasible in resource poor settings, but it definitely improves the pregnancy outcomes considering the high prevalence of gestational diabetes in India.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Lei Liu ◽  
Jiajin Hu ◽  
Liu Yang ◽  
Ningning Wang ◽  
Yang Liu ◽  
...  

Background. Obese women with gestational diabetes mellitus (GDM) have a higher risk of adverse outcomes than women with obesity or GDM alone. Our study is aimed at investigating the discriminatory power of circulatory Wnt1-inducible signaling pathway protein-1 (WISP1), a novel adipocytokine, on the copresence of prepregnancy overweight/obesity and GDM and at clarifying the relationship between the WISP1 level and clinical cardiometabolic parameters. Methods. A total of 313 participants were screened from a multicenter prospective prebirth cohort: Born in Shenyang Cohort Study (BISCS). Subjects were examined with a 2×2 factorial design for body mass index BMI≥24 and GDM. Between 24 and 28 weeks of pregnancy, follow-up individuals underwent an OGTT and blood sampling for cardiometabolic characterization. Results. We observed that the WISP1 levels were elevated in prepregnancy overweight/obesity patients with GDM, compared with nonoverweight subjects with normal blood glucose (3.45±0.89 vs. 2.91±0.75 ng/mL). Multilogistic regression analyses after adjustments for potential confounding factors revealed that WISP1 was a strong and independent risk factor for prepregnancy overweight/obesity with GDM (all ORs>1). In addition, the results of the ROC analysis indicated that WISP1 exhibited the capability to identify individuals with prepregnancy overweight/obesity and GDM (all AUC>0.5). Finally, univariate and multivariate linear regression showed that WISP1 level was positively and independently correlated with fasting blood glucose, systolic blood pressure, and aspartate aminotransferase and was negatively correlated with HDL-C and complement C1q. Conclusions. WISP1 may be critical for the prediction, diagnosis, and therapeutic strategies against obesity and GDM in pregnant women.


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