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

• Published in: International Journal of Obesity 2024-03, Vol.48 (3), p.403-413
• Main Authors: Kunte, Pooja, Barberio, Matthew, Tiwari, Pradeep, Sukla, Krishna, Harmon, Brennan, Epstein, Samuel, Bhat, Dattatray, Authelet, Kayla, Goldberg, Madeleine, Rao, Sudha, Damle, Hemant, Freishtat, Robert J., Yajnik, Chittaranjan
• Format: Article
• Language: English
• Subjects: 38/39; 45/61; 692/163/2743/2037; 692/163/2743/393; Adipocytes; Adipose tissue; Adiposity - genetics; Blood plasma; Body Mass Index; Body size; Cord blood; Diabetes mellitus; Diabetes, Gestational; Epidemiology; Female; Fetal Blood - metabolism; Fetuses; Folic acid; Forkhead protein; Growth factors; Health Promotion and Disease Prevention; Humans; Hyperglycemia; Hyperglycemia - metabolism; Infant, Newborn; Internal Medicine; Kinases; Male; MAP kinase; Medicine; Medicine & Public Health; Metabolic Diseases; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Neonates; Obesity - metabolism; Pregnancy; Pregnancy complications; Public Health; Transcription factors; Transforming growth factor-b; Vitamin B12
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/s41366-023-01432-z

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 There were 279 mother-neonate pairs with all phenotypic data (normal glucose tolerant NGT = 148, gestational diabetes mellitus GDM = 131). Neonates with adiposity were those in the highest tertile (T3) of sex-specific sum of skinfolds and those without adiposity (lean) in the lowest tertile T1 of NGT pregnancies. We studied ADsEV miRNAs in 76 and 51 neonates with and without adiposity respectively and their mothers based on power calculations (68 NGT and 59 GDM pregnancies). ADsEV miRNAs from maternal and cord blood plasma samples were profiled on Agilent 8*60 K microarray. Differential expression (DE) of ADsEV miRNAs in adipose vs. lean groups was studied before and after adjustment for maternal 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 (discovery p ≤ 0.1) in the adipose group in unadjusted, 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 ADsEV miRNAs in mothers are potential regulators of fetal adiposity. The expression and functionality of miRNAs appear to be influenced by maternal adiposity, hyperglycemia, and micronutrient status during pregnancy.