miR-1-3p and miR-133-3p are altered in maternal serum EVs and placenta in pregnancies complicated by gestational diabetes with large-for-gestational age babies

Kennedy, Margeurite; Cartland, Sarah J.; Saravanan, Ponnusamy; Simpson, Nigel; Scott, Eleanor M.; Forbes, Karen

doi:10.1530/endoabs.65.p349

Cited by 2 publications

(6 citation statements)

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Section: Discussionsupporting

confidence: 89%

“…With regard to miR-1-3p, our study produced supportive findings to the study of Kennedy et al [233], in which they reported increased levels of miR-1-3p in serum extracellular vesicles in patients with confirmed GDM diagnoses within 26-28 gestational weeks that subsequently delivered large-for-gestational-age new-borns (LGA) when compared with appropriately grown-for-gestational-age new-borns (AGA). Nevertheless, our data concerning miR-133a-3p and miR-145-5p are inconsistent with the study of Kennedy et al [233]. While they observed reduced levels of miR-145-5p and increased levels of miR-133a-3p in GDM pregnancies delivering LGA new-borns, we did not detect any changes in the gene expression of miR-133a-3p and miR-145-5p during the early stages of gestation in pregnancies destinated to develop GDM.…”

Section: Discussionsupporting

confidence: 89%

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Cardiovascular Disease-Associated MicroRNAs as Novel Biomarkers of First-Trimester Screening for Gestational Diabetes Mellitus in the Absence of Other Pregnancy-Related Complications

Hromadníková

Kotlabova

Krofta

2022

IJMS

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We assessed the diagnostic potential of cardiovascular disease-associated microRNAs for the early prediction of gestational diabetes mellitus (GDM) in singleton pregnancies of Caucasian descent in the absence of other pregnancy-related complications. Whole peripheral venous blood samples were collected within 10 to 13 weeks of gestation. This retrospective study involved all pregnancies diagnosed with only GDM (n = 121) and 80 normal term pregnancies selected with regard to equality of sample storage time. Gene expression of 29 microRNAs was assessed using real-time RT-PCR. Upregulation of 11 microRNAs (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-23a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-181a-5p, miR-195-5p, miR-499a-5p, and miR-574-3p) was observed in pregnancies destinated to develop GDM. Combined screening of all 11 dysregulated microRNAs showed the highest accuracy for the early identification of pregnancies destinated to develop GDM. This screening identified 47.93% of GDM pregnancies at a 10.0% false positive rate (FPR). The predictive model for GDM based on aberrant microRNA expression profile was further improved via the implementation of clinical characteristics (maternal age and BMI at early stages of gestation and an infertility treatment by assisted reproductive technology). Following this, 69.17% of GDM pregnancies were identified at a 10.0% FPR. The effective prediction model specifically for severe GDM requiring administration of therapy involved using a combination of these three clinical characteristics and three microRNA biomarkers (miR-20a-5p, miR-20b-5p, and miR-195-5p). This model identified 78.95% of cases at a 10.0% FPR. The effective prediction model for GDM managed by diet only required the involvement of these three clinical characteristics and eight microRNA biomarkers (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-100-5p, miR-125b-5p, miR-195-5p, miR-499a-5p, and miR-574-3p). With this, the model identified 50.50% of GDM pregnancies managed by diet only at a 10.0% FPR. When other clinical variables such as history of miscarriage, the presence of trombophilic gene mutations, positive first-trimester screening for preeclampsia and/or fetal growth restriction by the Fetal Medicine Foundation algorithm, and family history of diabetes mellitus in first-degree relatives were included in the GDM prediction model, the predictive power was further increased at a 10.0% FPR (72.50% GDM in total, 89.47% GDM requiring therapy, and 56.44% GDM managed by diet only). Cardiovascular disease-associated microRNAs represent promising early biomarkers to be implemented into routine first-trimester screening programs with a very good predictive potential for GDM.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 89%

Cardiovascular Disease-Associated MicroRNAs as Novel Biomarkers of First-Trimester Screening for Gestational Diabetes Mellitus in the Absence of Other Pregnancy-Related Complications

Hromadníková

Kotlabova

Krofta

2022

IJMS

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“…are also altered in EVs in both maternal circulation and placenta in GDM pregnancies that go on to deliver LGA babies (Kennedy et al, 2019) supports this hypothesis. Although further work is required to confirm this, a potential role for EV miRNAs in pathogenesis of GDM and associated fetal growth could provide both novel diagnostic and therapeutic opportunities to reduce clinical burden associated with GDM.…”

Section: Extracellular Vesicles In Obstetric Diseasesmentioning

confidence: 52%

“…Given that placental vascular dysfunction is a feature of GDM, it is possible that these circulating EV‐enclosed miRNAs may contribute to placental dysfunction in GDM. Indeed our recent observation that vascular regulatory miRNAs are also altered in EVs in both maternal circulation and placenta in GDM pregnancies that go on to deliver LGA babies (Kennedy et al., 2019) supports this hypothesis. Although further work is required to confirm this, a potential role for EV miRNAs in pathogenesis of GDM and associated fetal growth could provide both novel diagnostic and therapeutic opportunities to reduce clinical burden associated with GDM.…”

Section: Introductionmentioning

confidence: 75%

“…pEVs have been shown to interact with maternal organs, influencing skeletal muscle biology (Kupper & Huppertz, 2022) and contributing to insulin resistance in the mother (Kandzija et al, 2019;Palma et al, 2022). Whilst the importance of pEVs in the pathogenesis of GDM is of obvious importance, there is also evidence that EVs in maternal circulation, and their miRNA cargo, could potentially influence placental development and dysfunction in GDM (Kennedy et al, 2019;Quilang et al, 2022). Gillet et al (2019) detected 10 maternal serum EV miRNAs that were upregulated in GDM at early gestation (6-15 weeks).…”

Section: Extracellular Vesicles In Obstetric Diseasesmentioning

confidence: 99%

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Extracellular vesicles as markers and mediators of pregnancy complications: gestational diabetes, pre‐eclampsia, preterm birth and fetal growth restriction

Farrelly

Kennedy

Spencer

et al. 2023

The Journal of Physiology

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In high income countries, approximately 10% of pregnancies are complicated by pre‐eclampsia (PE), preterm birth (PTB), fetal growth restriction (FGR) and/or macrosomia resulting from gestational diabetes (GDM). Despite the burden of disease this places on pregnant people and their newborns, there are still few, if any, effective ways of preventing or treating these conditions. There are also gaps in our understanding of the underlying pathophysiologies and our ability to predict which mothers will be affected. The placenta plays a crucial role in pregnancy, and alterations in placental structure and function have been implicated in all of these conditions. As extracellular vesicles (EVs) have emerged as important molecules in cell‐to‐cell communication in health and disease, recent research involving maternal‐ and placental‐derived EV has demonstrated their potential as predictive and diagnostic biomarkers of obstetric disorders. This review will consider how placental and maternal EVs have been investigated in pregnancies complicated by PE, PTB, FGR and GDM and aims to highlight areas where further research is required to enhance the management and eventual treatment of these pathologies. image

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miR-1-3p and miR-133-3p are altered in maternal serum EVs and placenta in pregnancies complicated by gestational diabetes with large-for-gestational age babies

Cited by 2 publications

References 0 publications

Cardiovascular Disease-Associated MicroRNAs as Novel Biomarkers of First-Trimester Screening for Gestational Diabetes Mellitus in the Absence of Other Pregnancy-Related Complications

Cardiovascular Disease-Associated MicroRNAs as Novel Biomarkers of First-Trimester Screening for Gestational Diabetes Mellitus in the Absence of Other Pregnancy-Related Complications

Extracellular vesicles as markers and mediators of pregnancy complications: gestational diabetes, pre‐eclampsia, preterm birth and fetal growth restriction

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