Cord blood exosomal miRNAS from small-for-gestational-age newborns associate with measures of subsequent catch-up growth and insulin resistance

Marta Diaz; Tania Quesada; Francesc Villarroya; Abel Lopez-Bermejo; Zegher Francis de; Lourdes Ibanez; Paula Casano-Sancho

doi:10.1530/endoabs.110.P683

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Endocrine Abstracts (2025) 110 P683 | DOI: 10.1530/endoabs.110.P683

ECEESPE2025 Poster Presentations MTEabolism, Nutrition and Obesity (125 abstracts)

Cord blood exosomal miRNAS from small-for-gestational-age newborns associate with measures of subsequent catch-up growth and insulin resistance

Marta Díaz^{1, 2}, Tania Quesada^{3, 4}, Francesc Villarroya^{3, 5}, Abel López-Bermejo⁶, Francis de Zegher⁷, Lourdes Ibáñez^{1, 2} & Paula Casano-Sancho^{1, 2}

Author affiliations

¹Endocrinology Department, Institut de Recerca Sant Joan de Déu, University of Barcelona, 08950 Esplugues, Barcelona, Spain; ²Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029, Madrid, Spain; ³Network Biomedical Research Center of Physiopathology of Obesity and Nutrition (CIBEROBN), Health Institute Carlos III, 28029, Madrid, Spain; ⁴Department of Biomedicine, Institut de Recerca Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; ⁵Biochemistry and Molecular Biomedicine Department, Institute of Biomedicine, University of Barcelona, and Institut de Recerca Sant Joan de Déu 08950, Esplugues, Barcelona, Spain; ⁶Pediatric Endocrinology Research Group, Girona Institute for Biomedical Research (IDIBGI), Faculty of Medicine, University of Girona., Dr. Josep Trueta Hospital, 17007 Girona, Spain., Girona, Spain; ⁷Leuven Research & Development, University of Leuven., Leuven, Belgium

JOINT2844

Introduction: Infants born small-for-gestational age [SGA, birth weight (BW) ≤-2 SD for gestational age (GA)] who experience marked catch-up growth are at risk for subsequent insulin resistance and body adiposity. The mechanisms underlying these associations are not fully delineated. Exosomes are extracellular vesicles mediating intercellular communication, and their cargo (including DNAs, RNAs and proteins) may contribute to altered crosstalk among tissues. We tested in SGA infants whether the profile of exosomal miRNAs at birth differs from that in AGA infants and, if so, whether differentially expressed miRNAs in SGA newborns associate with measures of catch-up growth and insulin resistance up to the postnatal ages of 4 and 12 months.

Subjects and Methods: miRNAs profile in cord blood-derived exosomes was assessed by high-throughput small-RNA sequencing in 10 SGA and 10 appropriate-for-gestational-age (AGA, birth weight between -1 SD and + 1 SD for GA) infants. Differentially expressed miRNAs with a log₂ fold change ≥2. 4 or ≤-2. 4 were validated by RT-qPCR in 40 AGA and 35 SGA infants and correlated with anthropometric, body composition (by DXA) and endocrine-metabolic [glucose, insulin, HOMA-IR] parameters at the postnatal ages of 4 and 12 months. Target genes prediction for all differentially regulated miRNAs was obtained with the miRSystem and enrichment analysis was performed using DAVID software.

Results: Six exosomal miRNAs were found to be differentially expressed in SGA infants who subsequently developed spontaneous catch-up growth; miR-1-3p, miR-133a-3p and miR-206 were down-regulated (all P <0. 0001 vs AGA) whereas miR-372-3p, miR-519d-3p and miR-1299 were up-regulated (P between 0. 03 and <0. 0001 vs AGA). The target genes of these miRNAs relate to insulin, RAP1, TGF-beta and neurotrophin signaling. Receiver operating characteristic (ROC) analysis disclosed that these miRNAs could distinguish SGA from AGA infants (0. 65<AUC<0. 99; P between 0. 03 and <0. 0001). The expression levels of these miRNAs associated with BMI and HOMA-IR at 4 and 12 months of age (P between 0. 01 and <0. 001). Up-regulated miRNAs in SGA newborns associated also with gains of total and abdominal fat during infancy (all P between 0. 05 and 0. 009).

Conclusion: The exosomal miRNA profile of SGA infants at birth was found to differ from that of AGA infants, and to associate with measures of catch-up growth, insulin resistance, and body adiposity into late infancy. Further follow-up will disclose to which extent these associations persist into childhood, puberty and adolescence.