In the last few years, it has been shown that extracellular vesicles (EVs), including small (sEVs) and large EVs (lEVs) play a key role in intercellular communication in both healthy and pathological conditions. Gestational diabetes (GDM), a pregnancy disease occurring in approximately 6-13% of all pregnancies, is one of the most common complications during gestation. Although the etiology of GDM remains largely unknown, there have been several studies indicating a potential involvement of EVs in impaired beta cell adaptations in GDM pregnancies. Therefore, in this study we evaluated the influence of maternal blood sEVs from healthy and GDM patients on different cellular responses of 1.1B4 pancreatic beta cell line. Maternal blood samples were collected from both healthy and GDM patients. A protocol for the enrichment of sEV population using ultracentrifugation was employed. The influence of maternal blood sEVs on 1.1B4 pancreatic beta cells proliferation, apoptosis, glucose consumption, and lactate production was evaluated. Maternal blood sEVs from healthy and GDM patients reduced 1.1B4 cell proliferation. This effect was greater with sEVs from GDM patients compared to healthy sEVs. 1.1B4 cells treated with sEVs from healthy patients had a higher glucose consumption and lactate production compared to those treated with GDM sEVs. Both GDM and healthy sEVs did not alter 1.1B4 apoptosis. Our study illustrates that maternal blood sEVs modulate the metabolism and proliferation of a beta cell line and that this effect is altered by sEVs from GDM patients. Further investigations are warranted in order to fully understand the influence of EVs on beta cell functions and the development of GDM

Fetomaternal communication plays a decisive role during pregnancy. Soluble factors, such as hormones and neuropeptides but also extracellular vesicles (EV) are transferred from the placenta to the maternal circulation. EVs are membrane-linked vesicles that are released by cells and play an important role in the intercellular communication. They can be classified into various classes including exosomes and microvesicles. EVs contain a multitude of molecules, such as proteins, lipids, nucleic acids and microRNAs (miRNAs), which can be taken up by target cells through a variety of mechanisms. They contribute to the communication between the placenta and maternal organs and cells, including the immune system. Placental miRNAs play an important role in the regulation of cell functions in the placenta but can also be transported into immune cells via EVs. Their uptake can influence the immune response and contribute to the development of fetomaternal immune tolerance. In pregnancy disorders an diseases the amount and composition of placental EVs in maternal blood can be altered. Therefore, they have the potential to be used as diagnostic markers for complications during pregnancy in the future.

Die fetomaternale Kommunikation spielt eine entscheidende Rolle während der Schwangerschaft. Dazu werden lösliche Faktoren wie Hormone und Neuropeptide, aber auch extrazelluläre Vesikel (EV) von der Plazenta in den mütterlichen Kreislauf abgegeben. EV sind membrangebundene Vesikel, die von Zellen freigesetzt werden und eine wichtige Rolle in der interzellulären Kommunikation spielen. Sie können in verschiedene Klassen eingeteilt werden, darunter Exosomen und Mikrovesikel. EV enthalten eine Vielzahl von Molekülen wie Proteine, Lipide, Nukleinsäuren und microRNAs (miRNAs), die durch verschiedene Mechanismen von Zielzellen aufgenommen werden können. EV tragen zur Kommunikation zwischen Plazenta und mütterlichen Organen und Zellen einschließlich des Immunsystems bei. Plazentare miRNAs spielen eine wichtige Rolle bei der Regulation von Zellfunktionen in der Plazenta, gelangen aber auch mittels EV in Immunzellen. Deren Aufnahme kann die Immunantwort beeinflussen und zur Entwicklung der maternofetalen Immuntoleranz beitragen. Bei Schwangerschaftsstörungen und -erkrankungen kann die Menge und Zusammensetzung plazentarer EV verändert sein. Daher haben sie das Potenzial, zukünftig als diagnostische Marker für Schwangerschaftskomplikationen genutzt zu werden.

Pregnancy pathologies including gestational diabetes, intrauterine fetal growth restriction, and pre-eclampsia are common and significantly increase the risk of poor pregnancy outcomes. Research to better understand the pathophysiology and improve diagnosis and treatment is therefore crucial. The ex vivo placenta perfusion model offers a unique system to study pregnancy pathology without the risk of harm to mother or fetus. The presence of a maternal and fetal circulation and intact villus tree, facilitates investigations into maternal-fetal transfer, altered hemodynamics and vascular reactivity in the human placenta. It also provides a platform to test novel therapeutic agents. Here we review the key studies which have utilized the ex vivo placenta perfusion model to study different aspects of such pregnancy pathologies.

Extracellular vesicles (EVs) released by the placenta are packed with biological information and play a major role in fetomaternal communication. Here, we describe a comprehensive set‐up for the enrichment and characterization of EVs from human placenta perfusion and their application in further assays.

Retinal angiogenesis is a hallmark of diabetic retinopathy. Matrix Metalloproteinases (MMPs) are involved in degradation of extracellular matrix (ECM). Functional SNP-1562C > T in the promoter of the MMP-9 gene results increase in transcriptional activity. The present work was designed to evaluate the contribution of functional SNP-1562C > T of MMP-9 gene to the risk of proliferative diabetic retinopathy (PDR) in type 2 diabetes mellitus (T2DM) patients in north Indian Population.This Case control study comprised of a total of 645 individuals in which 320 were T2DM patients out of which 73 had PDR, 98 had non- proliferative diabetic retinopathy (NPDR), 149 T2DM cases without any eye related disease (DM) and 325 non diabetic healthy individuals as controls (non DM controls). Genotyping for SNP-1562C > T of MMP-9 was done by polymerase chain reactions followed by restriction analyses with specific endonucleases (PCR-RFLP). DNA sequencing was used to ascertain PCR-RFLP results.T allele frequency in PDR patients was 32.1%, 20.4% in NPDR, 15.4% in DM and 13.7% in controls. Statistically significant difference was observed in both allele and genotype distribution between the PDR versus non-DM control group (p < 0.0001 by T allele; p = 0.002 by TT and p < 0.0001 by CT genotype).The present study suggests that the functional SNP-1562C > T in the promoter of the MMP-9 gene could be regarded as a major risk factor for PDR as increased MMP-9 production from high expressing T allele may promote retinal angiogenesis.