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Risk Factors and Molecular Mechanisms of Gestational Diabetes II
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Risk Factors and Molecular Mechanisms of Gestational Diabetes II

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 April 2020) | Viewed by 12426

Special Issue Editor

Dr. Vernon W. Dolinsky

E-Mail Website
Guest Editor
Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme of the Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada
Interests: diabetes; obesity; heart disease; fetal programming; mitochondria; epigenetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gestational diabetes mellitus (GDM) is one of the most common pregnancy-related health conditions, affecting 5–10% of pregnant women; however, even higher incidences are reported among some ethnicities. In addition, GDM is rising in the population. The majority of women who develop GDM have peripheral insulin resistance related to being overweight and obese, although GDM can also occur in the absence of obesity. GDM increases the risk for the development of type 2 diabetes and cardiovascular disease in women. Beyond its effects on maternal health, GDM also has serious health implications for the offspring. GDM is associated with elevated incidence of complications during delivery, fetal postpartum hypoglycemia, and congenital defects. In addition, GDM is associated with altered fetal growth as well as obesity, type 2 diabetes (T2D), and heart disease in the offspring as they age. Considerable interest is focused on finding biomarkers and mechanisms that explain GDM risk, as well as the mechanisms that condition the offspring for an increased risk of disease. This Special Issue of the International Journal of Molecular Sciences, “Risk Factors and Molecular Mechanisms of Gestational Diabetes” will focus on biomarkers and mechanisms in humans and animal model research. Authors are invited to submit manuscripts that address risk factors, biomarkers, and mechanisms of GDM development and their impact on their offspring. In addition, authors may also discuss therapies and interventions for GDM that are focused on improving the health of women and their children exposed to GDM.

Dr. Vernon W. Dolinsky
Guest Editor

Manuscript Submission Information

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Keywords

  • Gestational diabetes
  • Maternal obesity
  • Insulin resistance
  • Metabolism
  • Epigenetics
  • Lifestyle interventions and therapeutics
  • Placenta
  • Newborn complications
  • Fetal programming

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Published Papers (3 papers)

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Research

15 pages, 4420 KiB  
Article
Cell Type- and Sex-Specific Dysregulation of Thyroid Hormone Receptors in Placentas in Gestational Diabetes Mellitus
by Julia Knabl, Lena de Maiziere, Rebecca Hüttenbrenner, Stefan Hutter, Julia Jückstock, Sven Mahner, Franz Kainer, Gernot Desoye and Udo Jeschke
Int. J. Mol. Sci. 2020, 21(11), 4056; https://doi.org/10.3390/ijms21114056 - 5 Jun 2020
Cited by 13 | Viewed by 2992
Abstract
Thyroid hormones are essential for development of trophoblasts and the fetus. They also regulate a wide range of metabolic processes. We investigated the influence of maternal gestational diabetes mellitus (GDM) on thyroid hormone receptor (THR) isoforms THRα1, THRα2, THRβ1 and THRβ2 of the [...] Read more.
Thyroid hormones are essential for development of trophoblasts and the fetus. They also regulate a wide range of metabolic processes. We investigated the influence of maternal gestational diabetes mellitus (GDM) on thyroid hormone receptor (THR) isoforms THRα1, THRα2, THRβ1 and THRβ2 of the human placenta in a sex- and cell-type specific manner. Term placental tissue was obtained from women with (n = 40) or without GDM (control; n = 40). THRs levels were measured by semi-quantitative immunohistochemistry and real-time qRT-PCR. We localized THR immunostaining in syncytiotrophoblast (SCT), which was the tissue with the strongest signal. Double immunofluorescence identified THR in decidual cells in the stroma and in extravillous cytotrophoblasts. GDM did not change THRα1 immunolabelling intensity in decidua, but was associated with a stronger immunolabelling in SCT compared to GDM (p < 0.05). The SCT difference of GDM vs. control was strongest (p < 0.01) in female placentas. THRα2 was only weakly present and immunolabelling was weaker (p < 0.05) in SCT of only male GDM placentas in comparison to male controls. THRβ1/β2 immunostaining was weak in all cell types without changes in GDM. However, more THRβ1/2 protein was present (p < 0.001) in male than female placentas. All these protein changes were paralleled by changes of THR transcript levels. The data show that THR are expressed in term trophoblast in relation to fetal sex. Maternal GDM influences predominantly THRα1 in SCT, with the strongest GDM effect in SCT of female placentas. Full article
(This article belongs to the Special Issue Risk Factors and Molecular Mechanisms of Gestational Diabetes II)
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14 pages, 12012 KiB  
Article
Placental Galectin-2 Expression in Gestational Diabetes: A Systematic, Histological Analysis
by Paula Hepp, Laura Unverdorben, Stefan Hutter, Christina Kuhn, Nina Ditsch, Eva Groß, Sven Mahner, Udo Jeschke, Julia Knabl and Helene H. Heidegger
Int. J. Mol. Sci. 2020, 21(7), 2404; https://doi.org/10.3390/ijms21072404 - 31 Mar 2020
Cited by 18 | Viewed by 3531
Abstract
Gestational diabetes mellitus (GDM) is the most common pregnancy-associated metabolic disorder that negatively impacts on the health of both mothers and their offspring in the long-term. The molecular mechanisms involved are not fully understood. As in other states of insulin resistance, a disproportionate [...] Read more.
Gestational diabetes mellitus (GDM) is the most common pregnancy-associated metabolic disorder that negatively impacts on the health of both mothers and their offspring in the long-term. The molecular mechanisms involved are not fully understood. As in other states of insulin resistance, a disproportionate immune response in GDM leads to a state of chronic low-grade inflammation. Galectin-2 exerts regulatory effects on different immune cells. This study investigated galectin-2 expression in the placenta of 40 GDM patients and 40 controls, in a sex-specific manner. Immunohistochemistry was used for semi-quantitative analysis of expression strength. The phenotypes of galectin-2 expressing cells were characterized through double immunofluorescence. We found a significant up-regulation of galectin-2 in the fetal syncytiotrophoblast, as well as in the maternal decidua of GDM placentas. Double staining showed a strong galectin-2 expression in extra villous trophoblast cells and fetal endothelial cells in GDM. These findings present the first systematic investigation of galectin-2 in GDM. The findings contribute to the emerging understanding of the role of immunomodulation and inflammation in GDM and of galectin-2 itself. This might also have implications for the long-term cardiovascular health of the offspring. Full article
(This article belongs to the Special Issue Risk Factors and Molecular Mechanisms of Gestational Diabetes II)
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17 pages, 3029 KiB  
Article
Altered Genome-Wide DNA Methylation in Peripheral Blood of South African Women with Gestational Diabetes Mellitus
by Stephanie Dias, Sumaiya Adam, Paul Rheeder, Johan Louw and Carmen Pheiffer
Int. J. Mol. Sci. 2019, 20(23), 5828; https://doi.org/10.3390/ijms20235828 - 20 Nov 2019
Cited by 23 | Viewed by 5390
Abstract
Increasing evidence implicate altered DNA methylation in the pathophysiology of gestational diabetes mellitus (GDM). This exploratory study probed the association between GDM and peripheral blood DNA methylation patterns in South African women. Genome-wide DNA methylation profiling was conducted in women with (n [...] Read more.
Increasing evidence implicate altered DNA methylation in the pathophysiology of gestational diabetes mellitus (GDM). This exploratory study probed the association between GDM and peripheral blood DNA methylation patterns in South African women. Genome-wide DNA methylation profiling was conducted in women with (n = 12) or without (n = 12) GDM using the Illumina Infinium HumanMethylationEPIC BeadChip array. Functional analysis of differentially methylated genes was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A total of 1046 CpG sites (associated with 939 genes) were differentially methylated between GDM and non-GDM groups. Enriched pathways included GDM-related pathways such as insulin resistance, glucose metabolism and inflammation. DNA methylation of the top five CpG loci showed distinct methylation patterns in GDM and non-GDM groups and was correlated with glucose concentrations. Of these, one CpG site mapped to the calmodulin-binding transcription activator 1 (CAMTA1) gene, which have been shown to regulate insulin production and secretion and may offer potential as an epigenetic biomarker in our population. Further validation using pyrosequencing and conducting longitudinal studies in large sample sizes and in different populations are required to investigate their candidacy as biomarkers of GDM. Full article
(This article belongs to the Special Issue Risk Factors and Molecular Mechanisms of Gestational Diabetes II)
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