Neonatal adiposity is associated with microRNAs in adipocyte-derived extracellular vesicles in maternal and cord blood

新生儿肥胖与母体和脐带血中脂肪细胞衍生的细胞外囊泡中的微小RNA有关

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作者:Pooja Kunte, Matthew Barbeno, Pradeep Tiwari, Krishna Sukla, Brennan Harmon, Samuel Epstein, Dattatray Bhat, Kayla Authelet, Madeleine Goldberg, Sudha Rao, Hemant Damle, Robert Freishtat, Chittaranjan Yajnik

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.

Conclusion

Our results suggest that the ADsEV miRNAs in mothers are potential regulators of fetal adiposity. The expression and functionality of miRNAs appears to be influenced by maternal adiposity, hyperglycemia, and micronutrient status during pregnancy.

Methods

We studied 127 mother-neonate pairs (51 lean and 76 adipose neonates, in 68 NGT and 59 GDM pregnancies). Adiposity refers to the highest tertile (T3) of sum of skinfolds in neonates of normal glucose tolerant (NGT) mothers, lean to the 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.

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