{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:34:49Z","timestamp":1791812089356,"version":"4.3.4"},"reference-count":70,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Circadian rhythm disruption (CRD), stemming from sleep disorders and\/or shift work, is a risk factor for reproductive dysfunction. CRD has been reported to disturb nocturnal melatonin signaling, which plays a crucial role in female reproduction as a circadian regulator and an antioxidant. The hypothalamic\u2010pituitary\u2010ovarian (HPO) axis regulates female reproduction, with luteinizing hormone (LH) pulse pattern playing a pivotal role in folliculogenesis and steroidogenesis. However, the effect of CRD on the HPO axis and the involvement of melatonin remains unclear. Female CBA\/CaJ mice underwent CRD modeling, which involves alternating between standard light conditions and an 8\u2010h advance schedule every 3 days for 8 weeks, whereas control mice were maintained under a standard 12:12\u2010h light\/dark (LD) cycle. Subsequent measurements of diurnal melatonin levels, LH pulse patterns assessments via serial tail\u2010tip blood sampling and evaluations of ovarian function were conducted. CRD altered the circadian rhythms of wheel\u2010running activity and melatonin secretion in mice and led to an augmented LH pulse pattern, evidenced by increased LH pulse frequency, mean LH levels, and pituitary <jats:italic>LH beta\u2010subunit (LH\u03b2)<\/jats:italic> expression, irregular estrous cycles, abnormal luteal function, altered endocrine function, and ovarian oxidative stress. Melatonin treatment (10\u2009mg\/kg\/day for 4 weeks) significantly improved the HPO axis disorder in CRD mice, decreasing the enhanced LH pulse frequency and pituitary <jats:italic>LH\u03b2<\/jats:italic> expression. These findings were further validated using an in vitro L\u03b2T2 cell perfusion model. Furthermore, melatonin restored ovarian function and scavenged reactive oxygen species, thereby preventing apoptosis and preserving ovarian function. This study offers new insights into the impact of CRD on the HPO axis and emphasizes the potential of melatonin supplementation in mitigating its effects on female reproduction.<\/jats:p>","DOI":"10.1111\/jpi.70026","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T09:50:02Z","timestamp":1736157002000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Melatonin Alleviates Circadian Rhythm Disruption\u2010Induced Enhanced Luteinizing Hormone Pulse Frequency and Ovarian Dysfunction"],"prefix":"10.1111","volume":"77","author":[{"given":"Yujing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology West China Second University Hospital of Sichuan University Chengdu Sichuan China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children Ministry of Education Sichuan University Chengdu Sichuan China"},{"name":"NHC Key Laboratory of Chronobiology West China School of Basic Medical Sciences &amp; 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