{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:08:31Z","timestamp":1759190911095,"version":"3.44.0"},"reference-count":77,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"unspecified","delay-in-days":271,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["J Dev Orig Health Dis"],"published-print":{"date-parts":[[2025]]},"abstract":"<jats:title>Abstract<\/jats:title>\n\t  <jats:p>Adverse prenatal conditions can induce intrauterine growth restriction (IUGR) and increase the risk of adulthood metabolic disease. Mechanisms underlying developmentally programmed metabolic disease remain unclear but may involve disrupted postnatal circadian rhythms and kisspeptin signalling. We investigated the impact of maternal hypoxia-induced IUGR on hypothalamic and hepatic expression of clock genes (<jats:italic>Bmal1<\/jats:italic>, <jats:italic>Per2<\/jats:italic> and <jats:italic>Reverb\u03b1<\/jats:italic>), metabolic genes (<jats:italic>Ppar\u03b1<\/jats:italic>, <jats:italic>Ppar\u03b3<\/jats:italic> and <jats:italic>Pgc1\u03b1<\/jats:italic>) and kisspeptin genes (<jats:italic>Kiss1<\/jats:italic> and <jats:italic>Kiss1r<\/jats:italic>) in adult offspring. Pregnant BALB\/c mice were housed in hypoxic conditions (10.5% oxygen) from gestational day 11 to 17.5 and then returned to normoxic conditions until term (gestational day \u223c 21). Control animals were housed in normoxic conditions throughout pregnancy. Offspring were weighed at birth. At 8 weeks of age, body, liver and brain tissues were collected and weighed. Relative clock gene, metabolic gene and kisspeptin signalling gene expression were measured using qPCR. The IUGR offspring were lighter at birth and remained lighter at 8 weeks but with higher brain relative to body weight. The IUGR offspring had decreased hypothalamic <jats:italic>Bmal1<\/jats:italic> and <jats:italic>Reverb\u03b1<\/jats:italic> expression, but unchanged hepatic clock gene expression and no change in hypothalamic or hepatic <jats:italic>Per2<\/jats:italic> expression, compared with Control offspring. This tissue-specific change in clock gene expression suggests circadian dysregulation. There were no IUGR-related changes to metabolic gene expression in the hypothalamus or liver, but IUGR offspring had increased hypothalamic <jats:italic>Kiss1r<\/jats:italic> expression. These results demonstrate IUGR offspring from hypoxia pregnancies show central circadian misalignment and potentially disrupted hypothalamic <jats:italic>Kiss1\/Kiss1r<\/jats:italic> signalling, which may contribute to developmentally programmed metabolic disease.<\/jats:p>","DOI":"10.1017\/s2040174425100214","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T11:16:48Z","timestamp":1759144608000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":0,"title":["Intrauterine growth restriction promotes hypothalamic circadian dysregulation in adult mouse offspring"],"prefix":"10.1017","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7071-5243","authenticated-orcid":false,"given":"Alexandra E.","family":"O\u2019Brien","sequence":"first","affiliation":[{"name":"The University of Western 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