Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions

: Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations.

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Ultrastructure of Placenta of Gravidas with Gestational Diabetes Mellitus

Obstetrics and Gynecology International ◽

10.1155/2015/283124 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 12

Author(s):

Qian Meng ◽

Li Shao ◽

Xiucui Luo ◽

Yingping Mu ◽

Wen Xu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Morphological Changes ◽

Basal Membrane ◽

Normal Pregnancy ◽

Placental Development ◽

Terminal Villi ◽

And Function ◽

And Control

Objectives. Gestational diabetes mellitus (GDM) leads to an abnormal placental environment which may cause some structural alterations of placenta and affect placental development and function. In this study, the ultrastructural appearances of term placentas from women with GDM and normal pregnancy were meticulously compared.Materials and Methods. The placenta tissues of term birth from 10 women with GDM and 10 women with normal pregnancy were applied with the signed informed consent. The morphology of fetomaternal interface of placenta was examined using light microscopy (LM) and transmission electron microscopy (TEM).Results. On LM, the following morphological changes in villous tissues were found in the GDM placentas when compared with the control placentas: edematous stroma, apparent increase in the number of syncytial knots, and perivillous fibrin deposition. On TEM, the distinct ultrastructural alterations indicating the degeneration of terminal villi were found in the GDM placentas as follows: thickening of the basal membrane (BM) of vasculosyncytial membrane (VSM) and the VSM itself, significantly fewer or even absent syncytiotrophoblastic microvilli, swollen or completely destroyed mitochondria and endoplasmic reticulum, and syncytiotrophoblasts with multiple vacuoles.Conclusion. Ultrastructural differences exist between GDM and control placentas. The differences of placenta ultrastructure are likely responsible for the impairment of placental barrier and function in GDM.

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miRNA Profiles in Extracellular Vesicles From Serum Early in Pregnancies Complicated by Gestational Diabetes Mellitus

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-02693 ◽

2019 ◽

Vol 104 (11) ◽

pp. 5157-5169 ◽

Cited By ~ 20

Author(s):

Virginie Gillet ◽

Annie Ouellet ◽

Yulia Stepanov ◽

Rodosthenis S Rodosthenous ◽

Erika Kathe Croft ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Differential Expression ◽

Extracellular Vesicles ◽

Placental Development ◽

Early Effect ◽

Reverse Transcription Pcr ◽

Underlying Mechanisms ◽

And Function

Abstract Context Underlying mechanisms leading to gestational diabetes mellitus (GDM) are still under investigation, and it is unclear whether the placenta plays a role in triggering glucose intolerance or if its functions are modified in response to the hyperglycemia. Circulating miRNAs are involved in placental development and function and are encapsulated in extracellular vesicles (EVs). Objective To compare differential expression of miRNAs in circulating EVs in pregnancies complicated by GDM vs controls. Methods This was a case-control study nested in a prospective pregnancy cohort including 23 women with GDM and 46 matched controls. The presence of serum EVs in early pregnancy was validated by transmission electron microscopy. Placental dimensions were assessed at 11 to 13 weeks of gestation. Differential expression of 17 miRNAs encapsulated in EVs (miR‒122-5p, miR‒132-3p, miR-1323, miR‒182-3p, miR‒210-3p, miR‒29a-3p, miR‒29b-3p, miR‒342-3p, miR‒517-5p, miR‒517a-3p, miR‒518b, miR-520h, miR‒525-5p, miR‒136-5p, miR‒342-3p, miR‒376c-5p, and miR‒494-3p) was assessed using quantitative reverse transcription PCR. Results EVs were present in the early phase of placentation (6 to 15 weeks of gestation) in both cases and controls. No differences were observed for placental dimensions and estimated placental volume between GDM and control groups. Ten miRNAs (miR‒122-5p; miR‒132-3p; miR‒1323; miR‒136-5p; miR‒182-3p; miR‒210-3p; miR‒29a-3p; miR‒29b-3p; miR‒342-3p, and miR-520h) showed significantly higher levels in GDM cases than in controls (P ≤ 0.05). Bioinformatics analysis showed that these miRNAs are involved in trophoblast proliferation/differentiation as well as in insulin secretion/regulation and glucose transport in pregnant women. Conclusion The miRNA content of blood EVs may be a promising avenue for studying the early effect of impaired glucose metabolism on placental development.

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1336-P: Trimethylamine N-Oxide Inhibits the Formation of Neutrophil Extracellular Traps to Regulate Placental Development in Gestational Diabetes Mellitus

Diabetes ◽

10.2337/db20-1336-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 1336-P

Author(s):

XIAOJING LIN ◽

XIAOLING HE ◽

XIAOQIU XIAO

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Neutrophil Extracellular Traps ◽

Placental Development ◽

Extracellular Traps

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Gestational Diabetes Mellitus and Infant Adiposity at Birth: A Systematic Review and Meta-Analysis of Therapeutic Interventions

Journal of Clinical Medicine ◽

10.3390/jcm10040835 ◽

2021 ◽

Vol 10 (4) ◽

pp. 835

Author(s):

Manoja P. Herath ◽

Jeffrey M. Beckett ◽

Andrew P. Hills ◽

Nuala M. Byrne ◽

Kiran D. K. Ahuja

Keyword(s):

Diabetes Mellitus ◽

Adipose Tissue ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Fat Mass ◽

Metabolic Disorders ◽

Later Life ◽

Therapeutic Interventions ◽

Increased Risk ◽

The Impact

Exposure to untreated gestational diabetes mellitus (GDM) in utero increases the risk of obesity and type 2 diabetes in adulthood, and increased adiposity in GDM-exposed infants is suggested as a plausible mediator of this increased risk of later-life metabolic disorders. Evidence is equivocal regarding the impact of good glycaemic control in GDM mothers on infant adiposity at birth. We systematically reviewed studies reporting fat mass (FM), percent fat mass (%FM) and skinfold thicknesses (SFT) at birth in infants of mothers with GDM controlled with therapeutic interventions (IGDMtr). While treating GDM lowered FM in newborns compared to no treatment, there was no difference in FM and SFT according to the type of treatment (insulin, metformin, glyburide). IGDMtr had higher overall adiposity (mean difference, 95% confidence interval) measured with FM (68.46 g, 29.91 to 107.01) and %FM (1.98%, 0.54 to 3.42) but similar subcutaneous adiposity measured with SFT, compared to infants exposed to normal glucose tolerance (INGT). This suggests that IGDMtr may be characterised by excess fat accrual in internal adipose tissue. Given that intra-abdominal adiposity is a major risk factor for metabolic disorders, future studies should distinguish adipose tissue distribution of IGDMtr and INGT.

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