MicroRNAs in adipocyte-derived extracellular vesicles in maternal and cord blood are related to neonatal adiposity

Background Maternal body size, nutrition, and hyperglycemia contribute to neonatal body size and composition. There is little information on maternal-fetal transmission of messages which influence fetal growth. We analyzed adipocyte-derived small extracellular vesicular (ADsEV) microRNAs in maternal and cord blood to explore their adipogenic potential. Methods We studied 127 mother-neonate pairs (51 lean and 76 adipose neonates, in 68 NGT and 59 GDM pregnancies). Adiposity refers to highest tertile (T3) of sum of skinfolds in neonates of normal glucose tolerant (NGT) mothers, lean to lowest tertile (T1). ADsEV miRNAs from maternal and cord blood samples were profiled on Agilent 8*60K microarray. Differential expression (DE) of ADsEV miRNAs in adipose vs. lean neonates was studied before and after adjustment for maternal gestational diabetes mellitus (GDM), adiposity, and vitamin B12-folate status. Results Multiple miRNAs were common in maternal and cord blood and positively correlated. We identified 24 maternal and 5 cord blood miRNAs differentially expressed (p≤0.1) in the adipose neonate group, and 19 and 26 respectively, in the adjusted analyses. Even though DE miRNAs were different in maternal and cord blood, they targeted similar adipogenic pathways (e.g., the forkhead box O (FOXO) family of transcription factors, mitogen-activated protein kinase (MAPK) pathway, transforming growth factor beta (TGF-β) pathway). Maternal GDM and adiposity were associated with many DE ADsEV miRNAs. Conclusion Our results suggest that the DE ADsEV miRNAs in mothers of adipose neonates are potential regulators of fetal adiposity. Further, the composition and functionality of miRNAs may be influenced by maternal hyperglycemia, adiposity, and micronutrient status during pregnancy. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study was funded by InDiaGDM grant of the Department of Biotechnology, New Delhi, India (BT/IN/Denmark/02/CSY/2014) and National Institute of Health (NIH), the U.S government (R21HD094127-01). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of King Edward Memorial Hospital Research Centre, Pune, India gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. * PMNS : Pune Maternal Nutrition Study PCS : Pune Children Study SSF : Sum of skin folds EV : Extracellular vesicles ADsEV : Adipocyte derived small extracellular vesicles GDM : Gestational diabetes mellitus NGT : Normal glucose tolerant FABP4 : Fatty acid binding protein 4 DE : miRNA Differentially expressed microRNA