Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Current Diabetes Reports
Published in: Current Diabetes Reports 5/2017

01-05-2017 | Diabetes and Pregnancy (MF Hivert, Section Editor)

MicroRNAs in Pregnancy and Gestational Diabetes Mellitus: Emerging Role in Maternal Metabolic Regulation

Authors: Cédrik Poirier, Véronique Desgagné, Renée Guérin, Luigi Bouchard

Published in: Current Diabetes Reports | Issue 5/2017

Login to get access

Abstract

Purpose of the Review

This review focuses on the recent emergence of microRNAs (miRNAs) as metabolic and developmental regulators in pregnancy and their role in the development of gestational diabetes mellitus (GDM). MiRNAs are short and stable RNA sequences that repress protein synthesis through interference with messenger RNA translation.

Recent Findings

The placenta produces numerous miRNAs with some of them being released in the maternal circulation. These miRNA genes are encoded into specific clusters and expressed preferentially by placental cells, in a time-dependent manner. They were shown to be dysregulated in plasma and placenta from women suffering from GDM and associated with pregnancy and birth-related outcomes.

Summary

The discovery of pregnancy-related miRNAs and their respective characterization will provide us with important information as to their function in maternal and placental metabolic regulation. More studies are needed to determine whether they will be useful for early screening of GDM.
Literature
1.
Sacks DA, et al. Frequency of gestational diabetes mellitus at collaborating centers based on IADPSG consensus panel-recommended criteria: the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. Diabetes Care. 2012;35(3):526–8.CrossRefPubMedPubMedCentral
2.
3.
4.
Ferrara A. Increasing prevalence of gestational diabetes mellitus: a public health perspective. Diabetes Care. 2007;30(Suppl 2):S141–6.CrossRefPubMed
5.
•• WHO, Report of the Commission on Ending Childhood Obesity. 2016, World Health Organization. A recent report from the World Health Organization documenting the current global epidemic of obesity and the establishment of an international initiative to stop what is now a crisis. The initiative recognizes the importance of monitoring and detecting gestational diseases (Non communicable) such as GDM.
6.
Barbour LA, et al. Cellular mechanisms for insulin resistance in normal pregnancy and gestational diabetes. Diabetes Care. 2007;30(Suppl 2):S112–9.CrossRefPubMed
7.
Robitaille J, Grant AM. The genetics of gestational diabetes mellitus: evidence for relationship with type 2 diabetes mellitus. Genet Med. 2008;10(4):240–50.CrossRefPubMed
8.
9.
Metzger BE, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010;33(3):676–82.CrossRefPubMed
10.
11.
Teede HJ, et al. Gestational diabetes: development of an early risk prediction tool to facilitate opportunities for prevention. Aust N Z J Obstet Gynaecol. 2011;51(6):499–504.CrossRefPubMed
12.
Lawrence JM, et al. Prevalence and timing of postpartum glucose testing and sustained glucose dysregulation after gestational diabetes mellitus. Diabetes Care. 2010;33(3):569–76.CrossRefPubMed
13.
Kim C, Berger DK, Chamany S. Recurrence of gestational diabetes mellitus: a systematic review. Diabetes Care. 2007;30(5):1314–9.CrossRefPubMed
14.
15.
Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–54.CrossRefPubMed
16.
• Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014;15(8):509–24. A very detailed and comprehensive review describing the genesis of microRNAs from the nucleus to the cytoplasm.
17.
Jonas S, Izaurralde E. Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet. 2015;16(7):421–33.CrossRefPubMed
18.
Lytle JR, Yario TA, Steitz JA. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR. Proc Natl Acad Sci U S A. 2007;104(23):9667–72.CrossRefPubMedPubMedCentral
19.
Forman JJ, Legesse-Miller A, Coller HA. A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence. Proc Natl Acad Sci U S A. 2008;105(39):14879–84.CrossRefPubMedPubMedCentral
20.
21.
22.
23.
24.
25.
Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation. Science. 2007;318(5858):1931–4.CrossRefPubMed
26.
Orom UA, Nielsen FC, Lund AH. MicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell. 2008;30(4):460–71.CrossRefPubMed
27.
Gupta SK, Bang C, Thum T. Circulating microRNAs as biomarkers and potential paracrine mediators of cardiovascular disease. Circ Cardiovasc Genet. 2010;3(5):484–8.CrossRefPubMed
28.
Zhu H, Fan GC. Extracellular/circulating microRNAs and their potential role in cardiovascular disease. Am J Cardiovasc Dis. 2011;1(2):138–49.PubMedPubMedCentral
29.
30.
Creemers EE, Tijsen AJ, Pinto YM. Circulating microRNAs: novel biomarkers and extracellular communicators in cardiovascular disease? Circ Res. 2012;110(3):483–95.CrossRefPubMed
31.
32.
Wienholds E, et al. MicroRNA expression in zebrafish embryonic development. Science. 2005;309(5732):310–1.CrossRefPubMed
33.
Gruber AJ, et al. Embryonic stem cell-specific microRNAs contribute to pluripotency by inhibiting regulators of multiple differentiation pathways. Nucleic Acids Res. 2014;42(14):9313–26.CrossRefPubMedPubMedCentral
34.
35.
Joglekar MV, Joglekar VM, Hardikar AA. Expression of islet-specific microRNAs during human pancreatic development. Gene Expr Patterns. 2009;9(2):109–13.CrossRefPubMed
36.
Krutzfeldt J, Stoffel M. MicroRNAs: a new class of regulatory genes affecting metabolism. Cell Metab. 2006;4(1):9–12.CrossRefPubMed
37.
Vienberg, S., et al., MicroRNAs in metabolism. Acta Physiol (Oxf), 2016.
38.
Weissgerber TL, Wolfe LA. Physiological adaptation in early human pregnancy: adaptation to balance maternal-fetal demands. Appl Physiol Nutr Metab. 2006;31(1):1–11.CrossRefPubMed
39.
Mastorakos G, Ilias I. Maternal and fetal hypothalamic-pituitary-adrenal axes during pregnancy and postpartum. Ann N Y Acad Sci. 2003;997:136–49.CrossRefPubMed
40.
41.
Herrera E, Desoye G. Maternal and fetal lipid metabolism under normal and gestational diabetic conditions. Horm Mol Biol Clin Investig. 2016;26(2):109–27.PubMed
42.
Ganss, R., Maternal metabolism and vascular adaptation in pregnancy: the PPAR link. Trends Endocrinol Metab, 2016.
43.
Ernst S, et al. Mechanisms in the adaptation of maternal beta-cells during pregnancy. Diabetes Manag (Lond). 2011;1(2):239–48.CrossRef
44.
45.
Morales-Prieto DM, et al. Pregnancy-associated miRNA-clusters. J Reprod Immunol. 2013;97(1):51–61.CrossRefPubMed
46.
• Morales-Prieto DM, et al. Elsevier Trophoblast Research Award Lecture: origin, evolution and future of placenta miRNAs. Placenta. 2014;35(Suppl):S39–45. Comprehensive review of the three most known clusters expressed preferentially by the placenta during pregnancy and their expression in different species related to humans. Also discusses the evolution of these clusters in eutherian species and interspecies differences in their expression as well as similarities (miRNA orthologs). CrossRefPubMed
47.
48.
49.
Mitchell MD, et al. Placental exosomes in normal and complicated pregnancy. Am J Obstet Gynecol. 2015;213(4 Suppl):S173–81.CrossRefPubMed
50.
• Rudov A, et al. Involvement of miRNAs in placental alterations mediated by oxidative stress. Oxidative Med Cell Longev. 2014;2014:103068. Comprehensive review highlighting the necessity of oxidative stress in the placentation process and that multiple pathologies have shown abnormalities in this process as well as associated miRNAs like miR-210. It describes this phenomenon as a potential contributor to GDM and subsequent placental injuries. CrossRef
51.
Noguer-Dance M, et al. The primate-specific microRNA gene cluster (C19MC) is imprinted in the placenta. Hum Mol Genet. 2010;19(18):3566–82.CrossRefPubMed
52.
•• Delorme-Axford E, et al. Human placental trophoblasts confer viral resistance to recipient cells. Proc Natl Acad Sci U S A. 2013;110(29):12048–53. This study demonstrates that the content (such as miRNAs) of placental exosomes are capable of conferring new properties to non placental cells. In this case, it was demonstrated that it promoted autophagy in recipient cells which later conferred them resistance to certain viral infections. This gives precedent to the notion of intercellular signalization by way of effector molecules like miRNAs and their potential role in the alteration of the maternal metabolism. CrossRefPubMedPubMedCentral
53.
Miura K, et al. Circulating levels of maternal plasma cell-free pregnancy-associated placenta-specific microRNAs are associated with placental weight. Placenta. 2014;35(10):848–51.CrossRefPubMed
54.
Hasegawa Y, et al. Increased levels of cell-free miR-517a and decreased levels of cell-free miR-518b in maternal plasma samples from placenta Previa pregnancies at 32 weeks of gestation. Reprod Sci. 2015;22(12):1569–76.CrossRefPubMed
55.
Hromadnikova I, et al. Circulating C19MC microRNAs in preeclampsia, gestational hypertension, and fetal growth restriction. Mediat Inflamm. 2013;2013:186041.
56.
Zhu XM, et al. Differential expression profile of microRNAs in human placentas from preeclamptic pregnancies vs normal pregnancies. Am J Obstet Gynecol. 2009;200(6):661 e1-7.CrossRefPubMed
57.
Miura, K., et al., Circulating levels of pregnancy-associated, placenta-specific microRNAs in pregnant women with placental abruption. Reprod Sci, 2016.
58.
Hromadnikova I, et al. Absolute and relative quantification of placenta-specific micrornas in maternal circulation with placental insufficiency-related complications. J Mol Diagn. 2012;14(2):160–7.CrossRefPubMed
59.
Ostlund I, Haglund B, Hanson U. Gestational diabetes and preeclampsia. Eur J Obstet Gynecol Reprod Biol. 2004;113(1):12–6.CrossRefPubMed
60.
Unek G, et al., The proliferation mechanism of normal and pathological human placentas. Histol Histopathol. 2016:11832.
61.
Morales-Prieto DM, et al. MicroRNA expression profiles of trophoblastic cells. Placenta. 2012;33(9):725–34.CrossRefPubMed
62.
63.
• Labialle S, et al. The miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 domain controls neonatal metabolic adaptation. EMBO J. 2014;33(19):2216–30. Demonstrates a new link between the maternally imprinted C14MC and its possible role in the maintenance of energy homeostasis. The deletion of the maternal C14MC in mouse knockout models displayed a neonatal lethality presumed to be linked to a dysregulation of the neonatal hepatic gene expression program. This study helps us understand the importance of miRNAs in embryologic processes and hints at their implication in metabolic programming. CrossRefPubMedPubMedCentral
64.
65.
66.
Voorhoeve PM, et al. A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell. 2006;124(6):1169–81.CrossRefPubMed
67.
Cho WJ, et al. miR-372 regulates cell cycle and apoptosis of ags human gastric cancer cell line through direct regulation of LATS2. Mol Cells. 2009;28(6):521–7.CrossRefPubMed
68.
Huang Q, et al. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol. 2008;10(2):202–10.CrossRefPubMed
69.
Houbaviy HB, Murray MF, Sharp PA. Embryonic stem cell-specific microRNAs. Dev Cell. 2003;5(2):351–8.CrossRefPubMed
70.
Gu Y, et al. Differential miRNA expression profiles between the first and third trimester human placentas. Am J Physiol Endocrinol Metab. 2013;304(8):E836–43.CrossRefPubMedPubMedCentral
71.
Hromadnikova I, et al. Expression profile of C19MC microRNAs in placental tissue in pregnancy-related complications. DNA Cell Biol. 2015;34(6):437–57.CrossRefPubMedPubMedCentral
72.
73.
Chim SS, et al. Detection and characterization of placental microRNAs in maternal plasma. Clin Chem. 2008;54(3):482–90.CrossRefPubMed
74.
Miura K, et al. Identification of pregnancy-associated microRNAs in maternal plasma. Clin Chem. 2010;56(11):1767–71.CrossRefPubMed
75.
Luo SS, et al. Human villous trophoblasts express and secrete placenta-specific microRNAs into maternal circulation via exosomes. Biol Reprod. 2009;81(4):717–29.CrossRefPubMed
76.
Salomon C, et al. A gestational profile of placental exosomes in maternal plasma and their effects on endothelial cell migration. PLoS One. 2014;9(6):e98667.CrossRefPubMedPubMedCentral
77.
Ludwig AK, Giebel B. Exosomes: small vesicles participating in intercellular communication. Int J Biochem Cell Biol. 2012;44(1):11–5.CrossRefPubMed
78.
Gabbay-Benziv R, Baschat AA. Gestational diabetes as one of the “great obstetrical syndromes”—the maternal, placental, and fetal dialog. Best Pract Res Clin Obstet Gynaecol. 2015;29(2):150–5.CrossRefPubMed
79.
Atay S, et al. Trophoblast-derived exosomes mediate monocyte recruitment and differentiation. Am J Reprod Immunol. 2011;65(1):65–77.CrossRefPubMed
80.
81.
Deiuliis JA. MicroRNAs as regulators of metabolic disease: pathophysiologic significance and emerging role as biomarkers and therapeutics. Int J Obes. 2016;40(1):88–101.CrossRef
82.
Slusarz A, Pulakat L. The two faces of miR-29. J Cardiovasc Med (Hagerstown). 2015;16(7):480–90.CrossRef
83.
Shi Z, et al. Differential expression of microRNAs in omental adipose tissue from gestational diabetes mellitus subjects reveals miR-222 as a regulator of ERalpha expression in estrogen-induced insulin resistance. Endocrinology. 2014;155(5):1982–90.CrossRefPubMed
84.
Zhao C, et al. MicroRNA-518d regulates PPARalpha protein expression in the placentas of females with gestational diabetes mellitus. Mol Med Rep. 2014;9(6):2085–90.PubMed
85.
86.
Floris I, et al. Gestational diabetes mellitus impairs fetal endothelial cell functions through a mechanism involving microRNA-101 and histone methyltransferase enhancer of zester homolog-2. Arterioscler Thromb Vasc Biol. 2015;35(3):664–74.CrossRefPubMed
87.
•• Zhu Y, et al. Profiling maternal plasma microRNA expression in early pregnancy to predict gestational diabetes mellitus. Int J Gynaecol Obstet. 2015;130(1):49–53. First study conducted in a GDM context using the NGS technology to characterize miRNA profiles in the maternal plasma. It provided confirmation that it was possible to find new miRNAs associated with GDM by using new sequencing methods. CrossRefPubMed
88.
Li J, et al. A microRNA signature in gestational diabetes mellitus associated with risk of macrosomia. Cell Physiol Biochem. 2015a;37(1):243–52.CrossRefPubMed
89.
90.
Forbes K, Westwood M. Maternal growth factor regulation of human placental development and fetal growth. J Endocrinol. 2010;207(1):1–16.CrossRefPubMed
91.
Tryggestad JB, et al. Influence of gestational diabetes mellitus on human umbilical vein endothelial cell miRNA. Clin Sci (Lond). 2016;130(21):1955–67.CrossRef
92.
Novikova DS, et al. AMP-activated protein kinase: structure, function, and role in pathological processes. Biochemistry (Mosc). 2015;80(2):127–44.CrossRef
93.
Short KR, et al. Lower resting energy expenditure and fat oxidation in Native American and Hispanic infants born to mothers with diabetes. J Pediatr. 2015;166(4):884–9.CrossRefPubMedPubMedCentral
94.
95.
Witwer KW. Circulating microRNA biomarker studies: pitfalls and potential solutions. Clin Chem. 2015;61(1):56–63.CrossRefPubMed
96.
Vambergue A, Fajardy I. Consequences of gestational and pregestational diabetes on placental function and birth weight. World J Diabetes. 2011;2(11):196–203.PubMedPubMedCentral
97.
Meijer HA, Smith EM, Bushell M. Regulation of miRNA strand selection: follow the leader? Biochem Soc Trans. 2014;42(4):1135–40.CrossRefPubMed
Metadata
Title
MicroRNAs in Pregnancy and Gestational Diabetes Mellitus: Emerging Role in Maternal Metabolic Regulation
Authors
Cédrik Poirier
Véronique Desgagné
Renée Guérin
Luigi Bouchard
Publication date
01-05-2017
Publisher
Springer US
Published in
Current Diabetes Reports / Issue 5/2017
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-017-0856-5

Other articles of this Issue 5/2017

Current Diabetes Reports 5/2017 Go to the issue

Immunology, Transplantation, and Regenerative Medicine (L Piemonti and V Sordi, Section Editors)

T-cell Metabolism as a Target to Control Autoreactive T Cells in β-Cell Autoimmunity

Obesity (J McCaffery, Section Editor)

Pharmacotherapy of Obesity: Clinical Trials to Clinical Practice

Hospital Management of Diabetes (A Wallia and JJ Seley, Section Editors)

Treatment of Diabetic Ketoacidosis (DKA)/Hyperglycemic Hyperosmolar State (HHS): Novel Advances in the Management of Hyperglycemic Crises (UK Versus USA)

Other Forms of Diabetes and Its Complications (JJ Nolan, Section Editor)

Diabetes in Cushing Disease

Microvascular Complications—Nephropathy (M Afkarian, Section Editor)

Precision Medicine Approaches to Diabetic Kidney Disease: Tissue as an Issue

Economics and Policy in Diabetes (ES Huang and AA Baig, Section Editors)

Population Health Management for Diabetes: Health Care System-Level Approaches for Improving Quality and Addressing Disparities
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits