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 ◽  
...  

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.

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 408
Author(s):  
Sumali S. Hewage ◽  
Xin Yu Hazel Koh ◽  
Shu E. Soh ◽  
Wei Wei Pang ◽  
Doris Fok ◽  
...  

(1) Background: Breastfeeding has been shown to support glucose homeostasis in women after a pregnancy complicated by gestational diabetes mellitus (GDM) and is potentially effective at reducing long-term diabetes risk. (2) Methods: Data from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study were analyzed to understand the influence of breastfeeding duration on long-term dysglycemia (prediabetes and diabetes) risk in women who had GDM in the index pregnancy. GDM and dysglycemia four to seven years postpartum were determined by the oral glucose tolerance test (OGTT). A Poisson regression model with a robust error variance was used to estimate incidence rate ratios (IRRs) for dysglycemia four to seven years post-delivery according to groupings of the duration of any breastfeeding (<1, ≥1 to <6, and ≥6 months). (3) Results: Women who had GDM during the index pregnancy and complete breastfeeding information and OGTT four to seven years postpartum were included in this study (n = 116). Fifty-one women (44%) had postpartum dysglycemia. Unadjusted IRRs showed an inverse association between dysglycemia risk and ≥1 month to <6 months (IRR 0.91; 95% confidence interval [CI] 0.57, 1.43; p = 0.68) and ≥6 months (IRR 0.50; 95% CI 0.27, 0.91; p = 0.02) breastfeeding compared to <1 month of any breastfeeding. After adjusting for key confounders, the IRR for the ≥6 months group remained significant (IRR 0.42; 95% CI 0.22, 0.80; p = 0.008). (4) Conclusions: Our results suggest that any breastfeeding of six months or longer may reduce long-term dysglycemia risk in women with a history of GDM in an Asian setting. Breastfeeding has benefits for mothers beyond weight loss, particularly for those with GDM.


Diabetes Care ◽  
2020 ◽  
Vol 43 (4) ◽  
pp. 793-798 ◽  
Author(s):  
Sylvia H. Ley ◽  
Jorge E. Chavarro ◽  
Mengying Li ◽  
Wei Bao ◽  
Stefanie N. Hinkle ◽  
...  

2010 ◽  
Vol 118 (08) ◽  
pp. 485-489 ◽  
Author(s):  
G. Seghieri ◽  
F. Tesi ◽  
A. De Bellis ◽  
R. Anichini ◽  
G. Fabbri ◽  
...  

2021 ◽  
Vol 10 (10) ◽  
pp. 2202
Author(s):  
Katrien Benhalima

The incidence of gestational diabetes mellitus (GDM) and overt diabetes in pregnancy is rising globally. GDM leads to increased risks for maternal and neonatal adverse pregnancy outcomes. In addition, GDM is also associated with an increased long-term metabolic risk in mothers and offspring [1]. Although much is known about GDM, evidence gaps persist. For instance, more research is needed on how to prevent GDM, on whether screening and treatment of GDM in early pregnancy are beneficial, on non-fasting biomarkers to screen for GDM, on new biomarkers to predict pregnancy complications, and on how to reduce the long-term metabolic risk in mothers and infants after delivery. To address this important health issue, the present Special Issue in the Journal of Clinical Medicine was dedicated to recent advances in the field of GDM. This Special Issue published 16 articles on this topic. [...]


Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Jiaxi Yang ◽  
Janet Rich-Edwards ◽  
Molin Wang ◽  
Wafaie W Fawzi ◽  
Cuilin Zhang ◽  
...  

Introduction: Identifying strategies to mitigate gradual long-term weight gain is critical for preventing obesity and its related chronic diseases, particularly for persons at high risk, such as women with a history of gestational diabetes mellitus (GDM). We prospectively examined the independent associations between lifestyle changes in mid-life with long-term weight change among women with and without a history of GDM. Hypothesis: We hypothesized that favorable improvements in lifestyle would be associated with less long-term weight gain, particularly among women with a history of GDM. Methods: We used data from the longitudinal Nurses’ Health Study II, with self-reported lifestyle, diet via food frequency questionnaire, and body weight updated every 2-4 years. We analyzed repeated 4-year changes of the following lifestyle factors among parous women after age 40: adherence to a healthy dietary pattern (Alternate Healthy Eating Index score [AHEI]), physical activity (MET-hrs/wk), moderate alcohol intake (servings/d), and non-smoking, in relation to concurrent 4-year change in body weight (lb). We used multivariable generalized estimating equation models to estimate the least-squares mean of 4-year weight change and 95% confidence interval (CI) for each lifestyle change category (e.g., decrease, remain stable, and increase). Results: Our analysis included 61,637 women, of which 3,444 (5.6%) had a history of GDM. Mean of repeated 4-year weight change after age 40 was 3.0 lb (SD=14.3). Improving diet was associated with favorable 4-year weight change, particularly among women with a history of GDM vs. without GDM (AHEI score change from low to high: -6.3 lb [CI: -9.3, -3.4] vs. -2.7 lb [CI: -3.2, -2.2], respectively; p-interaction=0.04). Increasing physical activity was associated with weight maintenance for GDM women only (MET-hrs/wk change from low to high: 0.6 lb [95% CI: -0.6, 1.7] vs. 2.0 lb [95% CI: 1.8, 2.2] for GDM vs. non-GDM, respectively; p-interaction=0.01). Reducing alcohol (decreased servings/d: 1.9 lb [95% CI: 1.2, 2.6] and 2.8 lb [95% CI: 2.6, 2.9] for GDM vs. non-GDM, respectively) and smoking cessation (recent quitter: 9.8 lb [95% CI: 7.1, 12.5] and 8.5 lb [95% CI: 8.0, 9.1] for GDM vs. non-GDM, respectively) were associated with similar patterns in weight change for women with and without prior GDM. Further, the joint association of improving both diet and physical activity from low to high was related to -12.3 lb (95% CI: -19.5, -5.0) and -6.1 lb (95% CI: -8.0, -4.2) of weight loss for GDM vs. non-GDM women, respectively. Conclusions: We observed that attainable improvements in diet quality and physical activity were associated with weight gain prevention. These findings support continued efforts to improve lifestyle as a beneficial strategy to prevent long-term weight gain, particularly among women with a history of GDM.


2019 ◽  
Vol 20 (6) ◽  
pp. 1408 ◽  
Author(s):  
Catalina Prieto ◽  
Bárbara Casas ◽  
Paulina Falcón ◽  
Andrea Villanueva ◽  
Pablo Lois ◽  
...  

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.


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