Metabolism-related microRNAs in maternal breast milk are influenced by premature delivery

Molly C Carney, Andrij Tarasiuk, Susan L DiAngelo, Patricia Silveyra, Abigail Podany, Leann L Birch, Ian M Paul, Shannon Kelleher, Steven D Hicks, Molly C Carney, Andrij Tarasiuk, Susan L DiAngelo, Patricia Silveyra, Abigail Podany, Leann L Birch, Ian M Paul, Shannon Kelleher, Steven D Hicks

Abstract

BackgroundMaternal breast milk (MBM) is enriched in microRNAs, factors that regulate protein translation throughout the human body. MBM from mothers of term and preterm infants differs in nutrient, hormone, and bioactive-factor composition, but the microRNA differences between these groups have not been compared. We hypothesized that gestational age at delivery influences microRNA in MBM, particularly microRNAs involved in immunologic and metabolic regulation.MethodsMBM from mothers of premature infants (pMBM) obtained 3-4 weeks post delivery was compared with MBM from mothers of term infants obtained at birth (tColostrum) and 3-4 weeks post delivery (tMBM). The microRNA profile in lipid and skim fractions of each sample was evaluated with high-throughput sequencing.ResultsThe expression profiles of nine microRNAs in lipid and skim pMBM differed from those in tMBM. Gene targets of these microRNAs were functionally related to elemental metabolism and lipid biosynthesis. The microRNA profile of tColostrum was also distinct from that of pMBM, but it clustered closely with tMBM. Twenty-one microRNAs correlated with gestational age demonstrated limited relationships with method of delivery, but not other maternal-infant factors.ConclusionPremature delivery results in a unique MBM microRNA profile with metabolic targets. This suggests that preterm milk may have adaptive functions for growth in premature infants.

Conflict of interest statement

Disclosure statement: Dr. Hicks holds a preliminary patent for microRNA biomarkers in autism spectrum disorder and serves as a consultant for Motion Intelligence, Inc. Dr. Kelleher serves as president and CEO of LactoGenix, Inc. These conflicts of interest are unrelated to the current manuscript and are under an active management plan by the Penn State College of Medicine.

Figures

Figure 1
Figure 1
Partial Least Squares Discriminant Analysis. A PLS DA of the total microRNA profile for pMBM (class 2, +, n=31), tMBM (class 3, ×, n=23) and tColostrum (class 0, ∆, n=10) achieved partial separation using two dimensions and accounted for 23.6% of the variance between samples.
Figure 2
Figure 2
Hierarchical clustering (HC) analysis. HC of the 20 miRNAs with the most significant changes across the three groups showed clustering of pMBM (class 2; n=31) from tMBM (class 3; n=23) and tColostrum (class 0; n=13). Note that tMBM fore milk (n=10) and hind milk (n=13) samples (denoted a and b respectively), as well as tMBM and tColostrum samples (taken from the same mother one month apart) were also spatially clustered. Gray scale values indicate average Z score of normalized abundance for each miRNA.
Figure 3
Figure 3
Pearson correlations. Heatmap visualization of Pearson’s correlation for the 26 miRNAs altered in lipid or skim pMBM demonstrates correlations between gestational age (as a continuous variable) and 21 miRNAs. Six of these miRNAs were correlated with delivery method, but no correlation was found between miRNAs and other variables. Color represents Pearson R values.

References

    1. Anderson GH, Atkinson SA, Bryan MH. Energy and macronutrient content of human milk during early lactation from mothers giving birth prematurely and at term. Am J Clin Nutr. 1981;34:258, 65.
    1. Lemons JA, Moye L, Hall D, et al. Differences in the composition of preterm and term human milk during early lactation. Pediatr Res. 1982;16:113–7.
    1. Aquilio E, Spagnoli R, Seri S, et al. Trace element content in human milk during lactation of preterm newborns. Biol Trace Elem Res. 1996;51:63–70.
    1. Schanler RJ, Lau C, Hurst NM, et al. Randomized trial of donor human milk versus preterm formula as substitutes for mothers’ own milk in the feeding of extremely premature infants. Pediatrics. 2005;116:400–6.
    1. Alsaweed M, Hartmann PE, Geddes DT, et al. MicroRNAs in breastmilk and the lactating breast: potential immunoprotectors and developmental regulators for the infant and the mother. International journal of environmental research and public health. 2015;12:13981–4020.
    1. Weber JA, Baxter DH, Zhang S, et al. The microRNA spectrum in 12 body fluids. Clin chem. 2010;56:1733–41.
    1. Muroya S, Hagi T, Kimura, et al. Lactogenic hormones alter cellular and extracellular microRNA expression in bovine mammary epithelial cell culture. Journal of animal science and biotechnology. 2016;7:8–18.
    1. Hassiotou F, Alsaweed M, Savigni D, et al. Profiling of Human Milk miRNA. FASEB J. 2015;29:582–8.
    1. Alsaweed M, Lai CT, Hartmann PE, et al. Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk. Scientific reports. 2016;6:1–13.
    1. Zhou Q, Li M, Wang X, et al. Immune-related microRNAs are abundant in breast milk exosomes. Int J Biol Sci. 2012;8:118–23.
    1. Alsaweed M, Ching TL, Hartmann PE, et al. Human milk cells contain numerous miRNAs that may change with milk removal and regulate multiple physiological processes. International Journal of Molecular Sciences. 2016;17:956–986.
    1. Rottiers V, Näär AM. MicroRNAs in metabolism and metabolic disorders. Nature reviews Molecular cell biology. 2012;13:239–50.
    1. Munch EM, Harris RA, Mohammad M, et al. Transcriptome profiling of microRNA by Next Gen deep sequencing reveals known and novel miRNA species in the lipid fraction of human breast milk. PLoS One. 2013;8:e50564.
    1. Arntz OJ, Pieters BC, Oliveira MC, et al. Oral administration of bovine milk derived extracellular vesicles attenuates arthritis in two mouse models. Molecular nutrition & food research. 2015;59:1701–12.
    1. Savage JS, Birch LL, Marini M, et al. Effect of the INSIGHT responsive parenting intervention on rapid infant weight gain and overweight status at age 1 year: a randomized clinical trial. JAMA pediatrics. 2016;170:742–49.
    1. Vlachos IS, Zagganas K, Paraskevopoulou MD, et al. DIANA miRPath v3. 0: deciphering microRNA function with experimental support. Nucleic Acids Res. 2015:gkv403.
    1. Szklarczyk D, Franceschini A, Wyder S, et al. STRING v10: protein protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015;43:D447–52.
    1. Walley AJ, Blakemore AI, Froguel P. Genetics of obesity and the prediction of risk for health. Hum Mol Genet. 2006;15:R124–30.
    1. Ikeda K, Horie Inoue K, Ueno T, et al. miR 378a 3p modulates tamoxifen sensitivity in breast cancer MCF 7 cells through targeting GOLT1A. Scientific reports. 2015;5:1–12.
    1. Gonul O, Aydin HH, Kalmis E, et al. Effects of Ganoderma lucidum (higher basidiomycetes) extracts on the miRNA profile and telomerase activity of the MCF 7 breast cancer cell line. International journal of medicinal mushrooms. 2015;17:231–39.
    1. Qin W, Tang Y, Yang N, et al. Potential role of circulating microRNAs as a biomarker for unexplained recurrent spontaneous abortion. Fertil and Steril. 2016;105:1247–54.
    1. Shah MY, Pan X, Fix LN, et al. 5-fluorouracil drug alters the microrna expression profiles in MCF-7 breast cancer cells. J Cell Physiol. 2011;226:1868–78.
    1. Matamala N, Vargas MT, González Cámpora R, et al. MicroRNA deregulation in triple negative breast cancer reveals a role of miR 498 in regulating BRCA1 expression. Oncotarget. 2016;7:20068–79.
    1. Zhang K, Zhao S, Wang Q, et al. Identification of micrornas in nipple discharge as potential diagnostic biomarkers for breast cancer. Ann Surg Oncol. 2015;22:536–44.
    1. Yang F, Zhang W, Shen Y, et al. Identification of dysregulated microRNAs in triple negative breast cancer. Int J Onc. 2015;46:927–32.
    1. Kumari A. Doctoral dissertation. 2014. Changes in microRNA target sites attributed to single nucleotide polymorphisms may influence breast cancer susceptibility.
    1. Maltseva DV, Galatenko VV, Samatov TR, et al. miRNome of inflammatory breast cancer. BMC research notes. 2014;7:871–81.
    1. Lingwood CA. Glycosphingolipid functions. Cold Spring Harbor perspectives in biology. 2011;3:a004788.
    1. van Meer G, Lisman Q. Sphingolipid transport: rafts and translocators. J Biol Chem. 2002;277:25855–58.
    1. Jiang M, Sang X, Hong Z. Beyond nutrients: Food-derived microRNAs provide cross- kingdom regulation. Bioessays. 2012;34:280–4.
    1. Arroyo JD, Chevillet JR, Kroh EM, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci USA. 2011;108:5003–8.
    1. Hill PD, Aldag JC, Demirtas H, et al. Association of serum prolactin and oxytocin with milk production in mothers of preterm and term infants. Biological research for nursing. 2009;10:340–9.
    1. Ferraro L, Ravo M, Nassa G, et al. Effects of oestrogen on microRNA expression in hormone responsive breast cancer cells. Hormones and Cancer. 2012;3:65–78.
    1. Cochrane DR, Spoelstra NS, Richer JK. The role of miRNAs in progesterone action. Mol Cell Endocrinol. 2012;357:50–9.
    1. Sethi JK, Hotamisligil GS. The role of TNFα in adipocyte metabolism. Seminars in cell & developmental biology. 1999;10:19–29.
    1. Wang L, Du Z, Liu J, et al. Association of UCP3, APN, and TNF-α Gene Polymorphisms with Type 2 Diabetes in a Population of Northern Chinese Han Patients. Chem Res Chinese Universities. 2012;28:255–8.
    1. Nisoli E, Tonello C, Landi M, et al. Functional studies of the first selective beta 3-adrenergic receptor antagonist SR 59230A in rat brown adipocytes. Mol Pharmacol. 1996;49:7–14.
    1. Lee MJ, Fried SK. The glucocorticoid receptor, not the mineralocorticoid receptor, plays the dominant role in adipogenesis and adipokine production in human adipocytes. International Journal of Obesity. 2014;38:1228–33.
    1. Culpin RE, Proctor SJ, Angus B, et al. A 9 series microRNA signature differentiates between germinal centre and activated B cell like diffuse large B cell lymphoma cell lines. Int J Oncol. 2010;37:367–77.
    1. Golding J, Emmett PM, Rogers IS. Gastroenteritis, diarrhoea and breast feeding. Early Hum Dev. 1997;49:S83–103.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel