lncRNA <em>NORAD</em> is consistently detected in breastmilk exosomes and its expression is downregulated in mothers of preterm infants

Mourtzi,Niki; Siahanidou,Tania; Tsifintaris,Margaritis; Karamichali,Eirini; Tasiopoulou,Androniki; Sertedaki,Amalia; Pesmatzoglou,Margarita; Kapetanaki,Anastasia; Liosis,George; Baltatzis,George; Vlachakis,Dimitrios; Chrousos,George P.; Giannakakis,Antonis

doi:10.3892/ijmm.2021.5049

lncRNA NORAD is consistently detected in breastmilk exosomes and its expression is downregulated in mothers of preterm infants

Authors:
- Niki Mourtzi
- Tania Siahanidou
- Margaritis Tsifintaris
- Eirini Karamichali
- Androniki Tasiopoulou
- Amalia Sertedaki
- Margarita Pesmatzoglou
- Anastasia Kapetanaki
- George Liosis
- George Baltatzis
- Dimitrios Vlachakis
- George P. Chrousos
- Antonis Giannakakis
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Affiliations: Laboratory of Molecular Endocrinology, Choremeio Research Center, First Department of Pediatrics, Children's Hospital ‘Aghia Sophia’, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece, First Department of Pediatrics, ‘Aghia Sophia’ Children's Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece, Laboratory of Gene Expression, Molecular Diagnostics and Modern Therapeutics, Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece, Laboratory of Molecular Virology, Hellenic Pasteur Institute, 11521 Athens, Greece, General and Maternity Hospital ‘Helena Venizelou’, 11521 Athens, Greece, First Department of Pathology, School of Health Sciences, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece, Laboratory of Genetics, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 11855 Athens, Greece, University Research Institute of Maternal and Child Health and Precision Medicine, and UNESCO Chair on Adolescent Health Care, National and Kapodistrian University of Athens, 11527 Athens, Greece
Published online on: October 14, 2021 https://doi.org/10.3892/ijmm.2021.5049
Article Number: 216
Copyright: © Mourtzi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast milk is the ideal food for infants and undoubtedly has immediate and long‑term benefits. Breast milk contains extracellular vesicles (EVs) i.e., exosomes secreted by maternal breast cells. Exosomes carry genetic material, such as long non‑coding RNAs (lncRNAs), which possibly participate in cell‑to‑cell communications, as they are known to regulate critical gene pathways. The aim of the present study was to screen human breastmilk exosomes for their lncRNA cargo and to examine exosomal lncRNA levels associated with milk obtained from mothers that gave birth at term or prematurely (<37 weeks of gestation). Samples were collected at 3 weeks postpartum from 20 healthy, breastfeeding mothers; 10 mothers had given birth at full‑term and 10 mothers preterm. Exosomal RNA was extracted from all samples and the expression of 88 distinct lncRNAs was determined using reverse transcription‑quantitative PCR. A total of 13 lncRNAs were detected in ≥85% of the samples, while 31 were detected in ≥50% of the samples. Differential expression analysis of the lncRNAs between the two groups revealed ≥2‑fold differences, with generally higher lncRNA concentrations found in the milk of the mothers that gave birth at term compared with those that gave birth preterm. Among these, the non‑coding RNA activated at DNA damage (NORAD) was prominently detected in both groups, and its expression was significantly downregulated in the breast milk exosomes of mothers who delivered preterm. On the whole, the present study demonstrates that breast milk lncRNAs may be important factors of normal early human development. Collectively, the presence of lncRNAs in human breast milk may explain the consistent inability of researchers to fully ‘humanize’ animal milk.

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