The Mystery of Exosomes in Gestational Diabetes Mellitus

Abstract

Gestational diabetes mellitus (GDM) is one of the common pregnancy complications, which increases the risk of short-term and long-term adverse consequences in both the mother and offspring. However, the pathophysiological mechanism of GDM is still poorly understood. Inflammation, insulin resistance and oxidative stress are considered critical factors in the occurrence and development of GDM. Although the lifestyle intervention and insulin are the primary treatment, adverse pregnancy outcomes still cannot be ignored. Exosomes have a specific function of carrying biological information, which can transmit information to target cells and play an essential role in intercellular communication. Their possible roles in normal pregnancy and GDM have been widely concerned. The possibility of exosomal cargos as biomarkers of GDM is proposed. This paper reviews the literature in recent years and discusses the role of exosomes in GDM and their possible mechanisms to provide some reference for the prediction, prevention, and treatment of GDM and improve the outcome of pregnancy.

Advances in Research on Aging in Female Infertility and Pathologic Pregnancy

“…Following the acclimation period of two weeks, the animals were randomly into three groups of six each as follows: Group I serves as the control and was given water and a regular chow diet ad lib for 66 days; group II was given oral gavage administration of letrozole (LETZ) (6 mg/kg bw) (3) for 21 days to induce PCOS and was left untreated for 45 days; For three weeks, Group III received oral gavage dose of LETZ (6 mg/kg), after which it received Quercetin (QUER) (125 mg/kg bw orally daily) for 45 days. We kept mice under normal ambient temperature (22-25˚C), relative humidity of (55)(56)(57)(58)(59)(60) and twelve hours of dark and light cycles respectively. A 50 mg/kg intraperitoneal dose of sodium pentobarbital was used to anaesthetize the mice and by puncturing the retro-orbital venous sinus, blood samples from all the mice were obtained at 66 th day of the experiment, and serum was obtained which was then used to analyse hormones and biochemistry.…”

Prospecting of exosomal-miRNA signatures as prognostic marker for gestational diabetes mellitus and other adverse pregnancy outcomes

“…Upregulation ofExomiR-16-5p in GDM patients during the second trimester, IRS1 and IRS2 are negatively regulated, thereby showing the effect of ExomiR-16-5p on these genes. This impairs Wnt signalling pathway and may ultimately result in GDM by blocking the autophagic degradation of Dishevelled 2 (45,48,49) which modulates a glycogen synthase kinase allowing nuclear translocation of beta-catenin and subsequent activation of Wnt-…”

“…ExomiR-16-5p regulates the PI3K/Akt, Wnt and mTOR signalling pathways, since these signalling pathways serve a key role in GDM ( 45 – 47 ). Upregulation ofExomiR-16-5p in GDM patients during the second trimester, IRS1 and IRS2 are negatively regulated, thereby showing the effect of ExomiR-16-5p on these genes.…”

“…Upregulation ofExomiR-16-5p in GDM patients during the second trimester, IRS1 and IRS2 are negatively regulated, thereby showing the effect of ExomiR-16-5p on these genes. This impairs Wnt signalling pathway and may ultimately result in GDM by blocking the autophagic degradation of Dishevelled 2 ( 45 , 48 , 49 ) which modulates a glycogen synthase kinase allowing nuclear translocation of beta-catenin and subsequent activation of Wnt-target gene. The placental mammalian target of rapamycin (mTOR) signal is activated by ExomiR-16-5p overexpression, which encourages mitochondrial function, protein synthesis and the transport of nutrients like amino acids, improving fetal nutrition utilisation.…”

“…Exosomes from GDM patients may therefore control placental nutritional capacity by stimulating the mTOR signal in the placental environment ( 50 ). It has been proposed that altered signalling of protein kinase B/Akt (Akt) and mTOR in human placental endothelial cells may be the cause of insulin resistance in pregnant women with GDM and their neonates ( 45 , 51 ).…”