{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:18:51Z","timestamp":1792109931592,"version":"4.4.0"},"reference-count":102,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intrauterine growth restriction (IUGR) is a risk factor for postnatal cardiovascular, metabolic, and psychiatric disorders. In most IUGR models, placental dysfunction that causes reduced 11\u03b2-hydroxysteroid dehydrogenase 2 (11\u03b2HSD2) activity, which degrades glucocorticoids (GCs) in the placenta, resulting in fetal GC overexposure. This overexposure to GCs continues to affect not only intrauterine fetal development itself, but also the metabolic status and neural activity in adulthood through epigenetic changes such as microRNA change, histone modification, and DNA methylation. We have shown that the IUGR model induced DNA hypomethylation in the paraventricular nucleus (PVN) in the brain, which in turn activates sympathetic activities, the renin\u2013angiotensin system (RAS), contributing to the development of salt-sensitive hypertension. Even in adulthood, strong stress and\/or exogenous steroids have been shown to induce epigenetic changes in the brain. Furthermore, DNA hypomethylation in the PVN is also observed in other hypertensive rat models, which suggests that it contributes significantly to the origins of elevated blood pressure. These findings suggest that if we can alter epigenetic changes in the brain, we can treat or prevent hypertension.<\/jats:p>","DOI":"10.3390\/ijms26010420","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T09:17:02Z","timestamp":1736155022000},"page":"420","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Fetal Environment and the Development of Hypertension\u2014The Epigenetic Modification by Glucocorticoids"],"prefix":"10.3390","volume":"26","author":[{"given":"Fumiko-Kawakami","family":"Mori","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Mitsui Memorial Hospital, Tokyo 101-8643, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8742-5129","authenticated-orcid":false,"given":"Tatsuo","family":"Shimosawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, School of Medicine, International University of Health and Welfare, Otawara 324-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1136\/bmj.298.6673.564","article-title":"Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease","volume":"298","author":"Barker","year":"1989","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0140-6736(89)90710-1","article-title":"Weight in infancy and death from ischaemic heart disease","volume":"2","author":"Barker","year":"1989","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1152\/physrev.00029.2013","article-title":"Early developmental conditioning of later health and disease: Physiology or pathophysiology?","volume":"94","author":"Hanson","year":"2014","journal-title":"Physiol. 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