{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T07:53:20Z","timestamp":1762070000658,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010067","name":"Gobierno de Aragon","doi-asserted-by":"publisher","award":["B19-20R"],"award-info":[{"award-number":["B19-20R"]}],"id":[{"id":"10.13039\/501100010067","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction: Smoking during pregnancy is associated with reduced foetal growth, amongst other effects. Epigenetic modification in the foetus and placenta during embryonic development as a result of changes in the function of miRNAs is one of the pathophysiological mechanisms responsible for this. This dysregulation may be due to environmental changes or toxins such as tobacco. Objective: To study the impact of smoking during pregnancy and its role in intrauterine growth restriction via hypermethylated miRNAs. Materials and methods: The differences in methylation patterns for miRNAs in umbilical cord blood from low-birth-weight newborns of smoking mothers were compared with those from normal-weight newborns using MedIP-seq (StarArray). Results: Seven hypermethylated miRNAs were identified in the epigenetic study of cord blood from low-birth-weight newborns of smoking mothers in our sample. The miRNAs found to be hypermethylated were: MIR7-1, MIR3918, MIR1244-1, MIR4721, MIR25, MIR93, MIR3656. Conclusion: Intrauterine exposure to tobacco induces hypermethylation-mediated miRNA silencing in low-birth-weight newborns by modifying the expression of factors involved in vascular development, growth, and adaptation to hypoxia.<\/jats:p>","DOI":"10.3390\/jcm11195808","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T23:39:31Z","timestamp":1665272371000},"page":"5808","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of miRNAs Involved in Foetal Growth Restriction Due to Maternal Smoking during Pregnancy"],"prefix":"10.3390","volume":"11","author":[{"given":"Eva","family":"Barrio","sequence":"first","affiliation":[{"name":"Facultad de Medicina, Universidad de Zaragoza, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alba","family":"Quir\u00f3s","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad de Zaragoza, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Lerma-Puertas","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad de Zaragoza, 50009 Zaragoza, Spain"},{"name":"Servicio de Obstetricia y Ginecolog\u00eda, Hospital Cl\u00ednico Universitario Lozano Blesa, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Labarta","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad de Zaragoza, 50009 Zaragoza, Spain"},{"name":"Unidad de Endocrinolog\u00eda, Servicio de Pediatr\u00eda, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0335-0404","authenticated-orcid":false,"given":"Ana","family":"Gasc\u00f3n-Catal\u00e1n","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Universidad de Zaragoza, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"ref_1","first-page":"56","article-title":"DNA methylation: An epigenetic process of medical importance","volume":"56","author":"Tancma","year":"2004","journal-title":"Rev. De Investig. Cl\u00edn."},{"key":"ref_2","first-page":"59","article-title":"Epigen\u00e9tica: Definici\u00f3n, bases moleculares e implicaciones en la salud y en la evoluci\u00f3n humana","volume":"10","author":"Garcia","year":"2012","journal-title":"Rev. Cienc. Salud"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1038\/nbt.1685","article-title":"Epigenetic modifications and human disease","volume":"28","author":"Portela","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_4","first-page":"66","article-title":"Epigen\u00e9tica: Vieja palabra, nuevos conceptos","volume":"51","author":"Juvenal","year":"2014","journal-title":"Rev. Argent. Endocrinol. Metab."},{"key":"ref_5","first-page":"529","article-title":"Epigen\u00e9tica, ciencia de la adaptaci\u00f3n biol\u00f3gica heredable","volume":"105","author":"Patricia","year":"2007","journal-title":"Arch. Argent. Pediatr\u00eda"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1210\/jc.2006-2017","article-title":"Management of the child born small for gestational age through to adulthood: A consensus statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society","volume":"92","author":"Clayton","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_7","first-page":"332","article-title":"Intrauterine growth retardation (IUGR): Epidemiology and etiology","volume":"6","author":"Javier","year":"2009","journal-title":"Pediatric Endocrinol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.1210\/jc.2004-1674","article-title":"The influence of cigarette smoking on antenatal growth, birth size, and the insulin-like growth factor axis","volume":"90","author":"Pringle","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1093\/hmg\/ddu739","article-title":"Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: Findings from the Avon Longitudinal Study of Parents and Children (ALSPAC)","volume":"24","author":"Richmond","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1289\/ehp.1205404","article-title":"Evaluation of the association between maternal smoking, childhood obesity, and metabolic disorders: A national toxicology program workshop review","volume":"121","author":"Behl","year":"2013","journal-title":"Environ. Health Perspect."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1289\/ehp.1408614","article-title":"Prenatal exposure to maternal cigarette smoking and DNA methylation: Epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age","volume":"123","author":"Lee","year":"2015","journal-title":"Environ. Health Perspect."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1261\/rna.068692.118","article-title":"Post-transcriptional control of miRNA biogenesis","volume":"25","author":"Michlewski","year":"2019","journal-title":"RNA"},{"key":"ref_13","first-page":"83","article-title":"Epigenetic studies in human diseases","volume":"56","author":"Haluskova","year":"2010","journal-title":"Folia Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41580-018-0059-1","article-title":"Regulation of microRNA biogenesis and its crosstalk with other cellular pathways","volume":"20","author":"Treiber","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1159\/000504669","article-title":"The Role of MicroRNAs in Influencing Body Growth and Development","volume":"93","author":"Cirillo","year":"2020","journal-title":"Horm. Res. Paediatr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1530\/JOE-19-0009","article-title":"Epigenetic responses and the developmental origins of health and disease","volume":"242","author":"Goyal","year":"2019","journal-title":"J. Endocrinol."},{"key":"ref_17","unstructured":"Hromadnikova, I., Kotlabova, K., Ondrackova, M., Kestlerova, A., Novotna, V., Hympanova, L., Doucha, J., and Krofta, L. (2022, July 26). Circulating C19MC microRNAs in Preeclampsia, Gestational Hypertension, and Fetal Growth Restriction, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/24347821\/."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"526","DOI":"10.4067\/S0717-75262016000600013","article-title":"Tabaquismo materno como factor posiblemente implicado en el desarrollo de la obesidad infantil","volume":"81","author":"David","year":"2016","journal-title":"Rev. Chil. Obstet. Ginecol."},{"key":"ref_19","first-page":"552","article-title":"Spanish cross-sectional growth study 2008. Part II. Height, weight and body mass index values from birth to adulthood","volume":"68","author":"Ruiz","year":"2008","journal-title":"An. Pediatr."},{"key":"ref_20","first-page":"544","article-title":"Spanish cross-sectional growth study 2008. Part I: Weight and height values in newborns of 26\u201342 weeks of gestational age","volume":"68","author":"Mendoza","year":"2008","journal-title":"An. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.ajhg.2016.02.019","article-title":"DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis","volume":"98","author":"Joubert","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12967-015-0384-5","article-title":"DNA methylation patterns in newborns exposed to tobacco in utero","volume":"13","author":"Ivorra","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.7150\/ijbs.27029","article-title":"The Pro-angiogenesis Of Exosomes Derived From Umbilical Cord Blood Of Intrauterine Growth Restriction Pigs Was Repressed Associated With MiRNAs","volume":"14","author":"Luo","year":"2018","journal-title":"Int. J. Biol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e18897","DOI":"10.1097\/MD.0000000000018897","article-title":"MicroRNA-206 predicts raised fetal growth retardation risk through the interaction with vascular endothelial growth factor in pregnancies","volume":"99","author":"Li","year":"2020","journal-title":"Medicine"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Loscalzo, G., Scheel, J., Iba\u00f1ez-Cabellos, J.S., Garc\u00eda-Lopez, E., Gupta, S., Garc\u00eda-Gimenez, J.L., Mena-Moll\u00e1, S., Perales-Mar\u00edn, A., and Morales-Rosell\u00f3, J. (2022). Overexpression of microRNAs miR-25-3p, miR-185-5p and miR-132-3p in Late Onset Fetal Growth Restriction, Validation of Results and Study of the Biochemical Pathways Involved. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010293"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Stepan, H., Galindo, A., Hund, M., Schlembach, D., Sillman, J., Surbek, D., and Vatish, M. (2022). Clinical utility of sFlt-1 and PlGF in screening, prediction, diagnosis and monitoring of pre-eclampsia and fetal growth restriction. Ultrasound Obstet. Gynecol., Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/35816445\/.","DOI":"10.1002\/uog.26032"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S1071","DOI":"10.1016\/j.ajog.2020.07.020","article-title":"First trimester preeclampsia screening and prediction","volume":"226","author":"Chaemsaithong","year":"2020","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1002\/uog.23669","article-title":"Routine first-trimester combined screening for pre-eclampsia: Pregnancy-associated plasma protein-A or placental growth factor?","volume":"58","author":"Guy","year":"2021","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_29","first-page":"151","article-title":"Hypoxia down-regulates placenta growth factor, whereas fetal growth restriction up-regulates placenta growth factor expression: Molecular evidence for \u201cplacental hyperoxia\u201d in intrauterine growth restriction","volume":"79","author":"Khaliq","year":"1999","journal-title":"Lab. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1007\/s11845-021-02664-6","article-title":"MiR-590-3p and its targets VEGF, PIGF, and MMP9 in early, middle, and late pregnancy: Their longitudinal changes and correlations with risk of fetal growth restriction","volume":"191","author":"Pei","year":"2022","journal-title":"Ir. J. Med. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ali, A., Hadlich, F., Abbas, M.W., Iqbal, M.A., Tesfaye, D., Bouma, G.J., Winger, A.Q., and Ponsuksili, S. (2021). Microrna\u2013mrna networks in pregnancy complications: A comprehensive downstream analysis of potential biomarkers. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052313"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Street, M.E., Grossi, E., Volta, C., Faleschini, E., and Bernasconi, S. (2008). Placental determinants of fetal growth: Identification of key factors in the insulin-like growth factor and cytokine systems using artificial neural networks. BMC Pediatr., 8.","DOI":"10.1186\/1471-2431-8-24"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1677\/joe.1.05781","article-title":"Altered expression of IGFs and IGF-binding proteins during intrauterine growth restriction in guinea pigs","volume":"184","author":"Carter","year":"2005","journal-title":"J. Endocrinol."},{"key":"ref_34","first-page":"91","article-title":"Insulin-like growth factors and their binding proteins in normal and abnormal human fetal growth","volume":"4","author":"Chard","year":"1994","journal-title":"Growth Regul."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Smerieri, A., Petraroli, M., Ziveri, M.A., Volta, C., Bernasconi, S., and Street, M.E. (2011). Effects of Cord Serum Insulin, IGF-II, IGFBP-2, IL-6 and Cortisol Concentrations on Human Birth Weight and Length: Pilot Study. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0029562"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1203\/00006450-199410000-00020","article-title":"Ontogeny of insulin-like growth factor-binding protein-1, -2, and -3: Quantitative measurements by radioimmunoassay in human fetal serum","volume":"36","author":"Bang","year":"1994","journal-title":"Pediatr. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Elsamadicy, E.A., and Thompson, L.P. (2022). Sex-Selective Increase of IGF-2 Expression in the Hypoxic Guinea Pig Placenta of Growth-Restricted Fetuses. Reprod. Sci., 1\u201311. Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/35616874\/.","DOI":"10.1007\/s43032-022-00979-y"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hu, X.-Q., and Zhang, L. (2019). MicroRNAs in Uteroplacental Vascular Dysfunction. Cells, 8, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/31671866\/.","DOI":"10.3390\/cells8111344"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s10456-018-9600-2","article-title":"miRNAs regulate the HIF switch during hypoxia: A novel therapeutic target","volume":"21","author":"Serocki","year":"2018","journal-title":"Angiogenesis"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1136\/bmj.301.6761.1111","article-title":"The fetal and infant origins of adult disease","volume":"301","author":"Barker","year":"1990","journal-title":"BMJ"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1136\/jech.58.2.114","article-title":"Developmental origins of adult health and disease","volume":"58","author":"Barker","year":"2004","journal-title":"J. Epidemiol. Community Health"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/19\/5808\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:44:19Z","timestamp":1760143459000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/19\/5808"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,30]]},"references-count":41,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["jcm11195808"],"URL":"https:\/\/doi.org\/10.3390\/jcm11195808","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2022,9,30]]}}}