MOLECULAR MECHANISMS OF THE FUNCTIONING SYSTEM MOTHER–PLACENTA–FETUS IN WOMEN WITH OBESITY AND GESTATIONAL DIABETES MELLITUS

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
I.I. Evsyukova
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Molecular Mechanisms

scholarly journals Downregulation of the Netrin-1 Receptor UNC5b Underlies Increased Placental Angiogenesis in Human Gestational Diabetes Mellitus

2019 ◽  
Vol 20 (6) ◽  
pp. 1408 ◽  
Author(s):  
Catalina Prieto ◽  
Bárbara Casas ◽  
Paulina Falcón ◽  
Andrea Villanueva ◽  
Pablo Lois ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factor ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Trophic Factors ◽  
High Blood Glucose ◽  
Glucose Levels ◽  
Placental Angiogenesis

Gestational diabetes mellitus (GDM) is a common metabolic disorder, defined by high blood glucose levels during pregnancy, which affects foetal and post-natal development. However, the cellular and molecular mechanisms of this detrimental condition are still poorly understood. A dysregulation in circulating angiogenic trophic factors, due to a dysfunction of the feto-placental unit, has been proposed to underlie GDM. But even the detailed study of canonical pro-angiogenic factors like vascular endothelial growth factor (VEGF) or basic Fibroblast Growth Factor (bFGF) has not been able to fully explain this detrimental condition during pregnancy. Netrins are non-canonical angiogenic ligands produced by the stroma have shown to be important in placental angiogenesis. In order to address the potential role of Netrin signalling in GDM, we tested the effect of Netrin-1, the most investigated member of the family, produced by Wharton’s Jelly Mesenchymal Stem Cells (WJ-MSC), on Human Umbilical Vein Endothelial Cells (HUVEC) angiogenesis. WJ-MSC and HUVEC primary cell cultures from either healthy or GDM pregnancies were exposed to physiological (5 mM) or high (25 mM) d-glucose. Our results reveal that Netrin-1 is secreted by WJ-MSC from healthy and GDM and both expression and secretion of the ligand do not change with distinct experimental glucose conditions. Noteworthy, the expression of its anti-angiogenic receptor UNC5b is reduced in GDM HUVEC compared with its expression in healthy HUVEC, accounting for an increased Netrin-1 signalling in these cells. Consistently, in healthy HUVEC, UNC5b overexpression induces cell retraction of the sprouting phenotype.

scholarly journals The Pathophysiology of Gestational Diabetes Mellitus

2018 ◽  
Vol 19 (11) ◽  
pp. 3342 ◽  
Author(s):  
Jasmine Plows ◽  
Joanna Stanley ◽  
Philip Baker ◽  
Clare Reynolds ◽  
Mark Vickers
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Overweight And Obesity ◽  
Chronic Hyperglycemia ◽  
Increased Risk

Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance due to pancreatic β-cell dysfunction on a background of chronic insulin resistance. Risk factors for GDM include overweight and obesity, advanced maternal age, and a family history or any form of diabetes. Consequences of GDM include increased risk of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth complications in the infant. There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies worldwide, and this number is set to increase with the escalating obesity epidemic. While several management strategies exist—including insulin and lifestyle interventions—there is not yet a cure or an efficacious prevention strategy. One reason for this is that the molecular mechanisms underlying GDM are poorly defined. This review discusses what is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration.

scholarly journals Differential Expression of MicroRNAs in Omental Adipose Tissue From Gestational Diabetes Mellitus Subjects Reveals miR-222 as a Regulator of ERα Expression in Estrogen-Induced Insulin Resistance

Endocrinology ◽  
2014 ◽  
Vol 155 (5) ◽  
pp. 1982-1990 ◽  
Author(s):  
Zhonghua Shi ◽  
Chun Zhao ◽  
Xirong Guo ◽  
Hongjuan Ding ◽  
Yugui Cui ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Differential Expression ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Luciferase Assay ◽  
Omental Adipose Tissue

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.

scholarly journals Histone H3 lysine 9 acetylation is downregulated in GDM Placentas and Calcitriol supplementation enhanced this effect

2018 ◽  
Vol 19 (12) ◽  
pp. 4061 ◽  
Author(s):  
Paula Hepp ◽  
Stefan Hutter ◽  
Julia Knabl ◽  
Simone Hofmann ◽  
Christina Kuhn ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Histone H3 ◽  
Western Blots ◽  
Specific Analysis ◽  
Villous Trophoblast ◽  
Rising Incidence

Despite the ever-rising incidence of Gestational Diabetes Mellitus (GDM) and its implications for long-term health of mothers and offspring, the underlying molecular mechanisms remain to be elucidated. To contribute to this, the present study’s objectives are to conduct a sex-specific analysis of active histone modifications in placentas affected by GDM and to investigate the effect of calcitriol on trophoblast cell’s transcriptional status. The expression of Histone H3 lysine 9 acetylation (H3K9ac) and Histone H3 lysine 4 trimethylation (H3K4me3) was evaluated in 40 control and 40 GDM (20 male and 20 female each) placentas using immunohistochemistry and immunofluorescence. The choriocarcinoma cell line BeWo and primary human villous trophoblast cells were treated with calcitriol (48 h). Thereafter, western blots were used to quantify concentrations of H3K9ac and the transcription factor FOXO1. H3K9ac expression was downregulated in GDM placentas, while H3K4me3 expression was not significantly different. Cell culture experiments showed a slight downregulation of H3K9ac after calcitriol stimulation at the highest concentration. FOXO1 expression showed a dose-dependent increase. Our data supports previous research suggesting that epigenetic dysregulations play a key role in gestational diabetes mellitus. Insufficient transcriptional activity may be part of its pathophysiology and this cannot be rescued by calcitriol.

scholarly journals Dietary supplementation of inulin alleviates metabolism disorders in gestational diabetes mellitus mice via RENT/AKT/IRS/GLUT4 pathway

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Miao Miao ◽  
Yongmei Dai ◽  
Can Rui ◽  
Yuru Fan ◽  
Xinyan Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Gestational Diabetes ◽  
Glucose Tolerance ◽  
Gestational Diabetes Mellitus ◽  
Glucose Homeostasis ◽  
Molecular Mechanisms ◽  
Fasting Blood Glucose ◽  
High Dose ◽  
Dependent Manner

Abstract Background Gestational diabetes mellitus (GDM) has significant short and long-term health consequences for both the mother and child. There is limited but suggestive evidence that inulin could improve glucose tolerance during pregnancy. This study assessed the effect of inulin on glucose homeostasis and elucidated the molecular mechanisms underlying the inulin-induced antidiabetic effects during pregnancy. Method Female C57BL/6 mice were randomized to receive either no treatment, high-dose inulin and low-dose inulin for 7 weeks with measurement of biochemical profiles. A real-time2 (RT2) profiler polymerase chain reaction (PCR) array involved in glycolipid metabolism was measured. Results Inulin treatment facilitated glucose homeostasis in a dose-dependent manner by decreasing fasting blood glucose, advanced glycation end products and total cholesterol, and improving glucose tolerance. Suppressing resistin (RETN) expression was observed in the inulin treatment group and the expression was significantly correlated with fasting blood glucose levels. The ratios of p-IRS to IRS and p-Akt to Akt in liver tissue and the ratio of p-Akt to Akt in adipose tissue as well as the expression level of GLUT4 increased significantly after inulin treatment. Conclusions Our findings indicated improvement of glucose and lipid metabolism by inulin was to activate glucose transport through the translocation of GLUT4 which was mediated by insulin signaling pathway repairment due to decreased expression of RETN and enhanced phosphorylation of IRS and Akt in GDM mice.

scholarly journals Compositional analysis of the bacterial community in colostrum samples from women with gestational diabetes mellitus and obesity

2020 ◽  
Author(s):  
July Stephany Gámez-Valdez ◽  
José Francisco García-Mazcorro ◽  
Alan Heriberto Montoya Rincón ◽  
Dalia Liliana Rodríguez Reyes ◽  
Gelacio Jiménez Blanco ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Maternal Obesity ◽  
Population Diversity ◽  
Vicious Cycle ◽  
Microbial Composition ◽  
The Impact

Abstract Background. Gestational Diabetes Mellitus (GDM) and obesity are threatening health conditions during pregnancy, as they affect the normal function of multiple systems, including neuro-hormonal networks, and adipose, liver, muscle and placenta. GDM and maternal obesity are main triggers to a vicious cycle of metabolic and cardiovascular diseases perpetuated trans-generationally. One of the first stages of this vicious cycle occurs during early lactation as the infant feeds of “disbalanced” breastmilk microbiota and macromolecule level. Despite the importance of breastmilk microbiota on newborn development, few studies have characterized breastmilk microbiota in association with obesity and GDM. Maternal obesity decreases the diversity of breastmilk microbiota, with increased proportions Staphylococcus compared to Bifidobacterium and Bacteroides. However, the extent to which GDM together with maternal obesity affect breastmilk microbiota is unknown. Here, we applied 16S-rRNA high-throughput sequencing to characterize colostrum microbiota of 43 mothers with exclusive GDM and obesity in order to address the impact of GDM/obesity on breastmilk microbiota.Results. We identified a total of 1,496 amplicon sequence variants (ASVs), being Proteobacteria and Firmicutes the dominant phyla. We found Staphylococcus, Corynebacterium-1, Anaerococcus and Prevotella overrepresented in samples of women with obesity and women with GDM. Population diversity indicators, such as Shannon/Faith phylogenetic index and UniFrac/robust Aitchison distances show distinct microbial composition for GDM (female-newborn subgroup) and obesity (male-newborn subgroup) compared to controls. Finally, Differential abundance analysis showed that Rhodobacteraceae was distinct for GDM and five families (Bdellovibrionaceae, Halomonadaceae, Shewanallaceae, Saccharimonadales and Vibrionaceae) were distinct for obesity groups.Conclusions. Our study indicates that GDM and obesity are related to a higher microbial diversity. Preliminary functional analysis suggests that this could be attributed to overrepresentation of amino acid and carbohydrate metabolism bacterial pathways. However, there is a strong influence of the infant´s gender and the utilization of antibiotics intrapartum. To our knowledge, this study represents the first characterization of the taxonomical changes of colostrum breastmilk in mothers with GDM. We think this study contributes to future design of functional metagenomic studies aiming to understand molecular mechanisms by which breastmilk from mothers with GDM/obesity affect the development and future adult physiology of their suckling infants.

Influence of maternal overnutrition and gestational diabetes on the programming of metabolic health outcomes in the offspring: experimental evidence

2015 ◽  
Vol 93 (5) ◽  
pp. 438-451 ◽  
Author(s):  
Troy J. Pereira ◽  
Brittany L. Moyce ◽  
Stephanie M. Kereliuk ◽  
Vernon W. Dolinsky
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Maternal Obesity ◽  
Obesity And Diabetes ◽  
Intergenerational Effect ◽  
Major Factors ◽  
Maternal Overnutrition

The incidence of obesity and type 2 diabetes mellitus have risen across the world during the past few decades and has also reached an alarming level among children. In addition, women are currently more likely than ever to enter pregnancy obese. As a result, the incidence of gestational diabetes mellitus is also on the rise. While diet and lifestyle contribute to these trends, population health data show that maternal obesity and diabetes during pregnancy during critical stages of development are major factors that contribute to the development of chronic disease in adolescent and adult offspring. Fetal programming of metabolic function, through physiological and (or) epigenetic mechanisms, may also have an intergenerational effect, and as a result may perpetuate metabolic disorders in the next generation. In this review, we summarize the existing literature that characterizes how maternal obesity and gestational diabetes mellitus contribute to metabolic and cardiovascular disorders in the offspring. In particular, we focus on animal studies that investigate the molecular mechanisms that are programmed by the gestational environment and lead to disease phenotypes in the offspring. We also review interventional studies that prevent disease with a developmental origin in the offspring.

scholarly journals Compositional Analysis Of The Bacterial Community In Colostrum Samples From Women With Gestational Diabetes Mellitus And Obesity

2020 ◽  
Author(s):  
July Stephany Gámez-Valdez ◽  
José Francisco García-Mazcorro ◽  
Alan Heriberto Montoya Rincón ◽  
Dalia Liliana Rodríguez Reyes ◽  
Gelacio Jiménez Blanco ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Compositional Analysis ◽  
Alpha Diversity ◽  
Newborn Health ◽  
Amplicon Sequencing ◽  
Shannon Index ◽  
Microbial Composition

Abstract Background. Obesity and Gestational Diabetes Mellitus (GDM) are major concerns during pregnancy as they compromise both mother and newborn health. These pathophysiology leads to variations in gut and breastmilk microbiota, threatening the settlement of neonate’s gut microbiota and the stimulation of immune cells. While several studies have described compositional changes of breast milk, placenta and maternal and newborn intestinal microbiota, it is unknown how breastmilk microbiota is affected under maternal GDM. The molecular mechanisms in which microbial-unbalanced breastmilk affect development of infants is not well understood for the case of obesity and GDM. As a first step, we used 16S- amplicon sequencing to describe the taxonomical bias of breastmilk of 43 women with GDM and women with obesity. We sampled colostrum within the first 24 h taken after birth in order to identify and quantify the first microbial community potentially colonizing infants gut.Results. A total of 1,675 amplicon sequence variants (ASVs) were identified, being Proteobacteria and Firmicutes the dominant phyla. We found Pseudomonas, Gemellales and Enterobacter overrepresented in samples of women with obesity and GDM. We used observed ASV´s, Shannon index and Faith´s phylogenetic diversity scores as alpha diversity indicators and UniFrac and robust Aitchison distances beta diversity indicators. Both metrics show a distinct microbial composition for GDM (female sub-group) and Obesity (male subgroup) compared to controls. Finally, differentially abundance analysis showed that Rhodococcaceae was distinct for GDM and 7 families (Bdellovibrionaceae, Burkholderiaceae, Halomonadaceae, Pseudomonadaceae, Shewanallaceae, TM7-1 and Vibrionaceae) with an absolute effect size greater than 1, of which 5 had a q-value ≤ 0.05 were distinct for obesity groups.Conclusions. To our knowledge, this study represents the first approach to the breastmilk bacteria composition of mothers with GDM. Our work provides the foundation for the design of functional metagnomic studies aiming to understand molecular mechanisms of which breastmilk from individuals with GDM and obesity affect the physiology of the infants.

scholarly journals Could gestational diabetes mellitus be managed through dietary bioactive compounds? Current knowledge and future perspectives

2016 ◽  
Vol 115 (7) ◽  
pp. 1129-1144 ◽  
Author(s):  
Carmela Santangelo ◽  
Alessandra Zicari ◽  
Elisabetta Mandosi ◽  
Beatrice Scazzocchio ◽  
Emanuela Mari ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Bioactive Compounds ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Virgin Olive Oil ◽  
Dietary Polyphenols ◽  
Insulin Signalling Pathway ◽  
Dietary Bioactive Compounds

AbstractGestational diabetes mellitus (GDM) is a serious problem growing worldwide that needs to be addressed with urgency in consideration of the resulting severe complications for both mother and fetus. Growing evidence indicates that a healthy diet rich in fruit, vegetables, nuts, extra-virgin olive oil and fish has beneficial effects in both the prevention and management of several human diseases and metabolic disorders. In this review, we discuss the latest data concerning the effects of dietary bioactive compounds such as polyphenols and PUFA on the molecular mechanisms regulating glucose homoeostasis. Several studies, mostly based onin vitroand animal models, indicate that dietary polyphenols, mainly flavonoids, positively modulate the insulin signalling pathway by attenuating hyperglycaemia and insulin resistance, reducing inflammatory adipokines, and modifying microRNA (miRNA) profiles. Very few data about the influence of dietary exposure on GDM outcomes are available, although this approach deserves careful consideration. Further investigation, which includes exploring the ‘omics’ world, is needed to better understand the complex interaction between dietary compounds and GDM.

scholarly journals Transcriptomic Profiling of Human Placenta in Gestational Diabetes Mellitus at the Single-Cell Level

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuqi Yang ◽  
Fang Guo ◽  
Yue Peng ◽  
Rong Chen ◽  
Wenbo Zhou ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Single Cell ◽  
Human Placenta ◽  
Molecular Mechanisms ◽  
Marker Genes ◽  
Specific Marker ◽  
Increased Risk ◽  
Adverse Pregnancy

Gestational diabetes mellitus (GDM) is associated with an increased risk of adverse pregnancy outcomes. Increasing evidence shows that placentation defects may play important roles in GDM. However, our understanding of the human placenta remains limited. In this study, we generated a comprehensive transcriptomic profile of cellular signatures and transcriptomes in the human placenta in GDM using single-cell RNA sequencing (scRNA-seq), constructed a comprehensive cell atlas, and identified cell subtypes and subtype-specific marker genes. In addition, we investigated the placental cellular function and intercellular interactions in GDM. These findings help to elucidate the molecular mechanisms of GDM, and may facilitate the development of new approaches to GDM treatment and prevention.

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