{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T10:53:06Z","timestamp":1764067986216,"version":"3.45.0"},"reference-count":94,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Food and Agriculture, U.S. Department of Agriculture, Hatch project","award":["1011100"],"award-info":[{"award-number":["1011100"]}]},{"name":"Agriculture and Food Research Initiative competitive grant","award":["2018-67016-27580"],"award-info":[{"award-number":["2018-67016-27580"]}]},{"DOI":"10.13039\/100007917","name":"U.S. Department of Agriculture, Agricultural Research Service","doi-asserted-by":"publisher","award":["6066-31000-015-00D"],"award-info":[{"award-number":["6066-31000-015-00D"]}],"id":[{"id":"10.13039\/100007917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study investigated the influence of maternal nutrient restriction and dietary melatonin supplementation on DNA methylation and gene expression in bovine placental cotyledons, with a focus on sex-specific changes. On day 160 of gestation, 29 Brangus heifers (bred to a single sire by AI) were subjected to a 2 \u00d7 2 factorial design: adequately fed (ADQ-CON, n = 7), nutrient-restricted (RES-CON, n = 7), and adequately fed or nutrient-restricted supplemented with 20 mg\/d of melatonin (ADQ-MEL, n = 7; RES-MEL, n = 8). Cotyledons were collected at day 240 from 12 female and 17 male conceptuses for Methyl MiniSeq-GWBS and RNA-Seq. In RES-CON vs. ADQ-CON, 93 hypomethylated and 143 hypermethylated DMRs were identified, primarily in exonic, intronic, and promoter regions. Melatonin altered the methylation patterns of male and female cotyledons, respectively, with 203 and 460 DMRs associated with axon guidance, RHOC GTPase cycle, and BDNF signaling pathways. RES-MEL showed higher expression of the UBOX5 gene compared with RES-CON. Moreover, 15 DEGs (5 upregulated and 10 downregulated) were observed in the male vs. female comparison. In melatonin-treated males, PIGX, ATP11C, snoRNA U2-19, ZNF82 genes were upregulated. Thus, melatonin may modulate conceptus growth and development in a sex-specific manner.<\/jats:p>","DOI":"10.3390\/ijms262311387","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T10:46:18Z","timestamp":1764067578000},"page":"11387","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Maternal Melatonin Supplementation Modulates Placental DNA Methylation and Gene Expression in Nutrient-Restricted Cattle"],"prefix":"10.3390","volume":"26","author":[{"given":"Shiveeli","family":"Rajput","sequence":"first","affiliation":[{"name":"Department of Animal and Dairy Sciences, Mississippi State University, Mississippi State, MS 39762, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brittni","family":"Littlejohn","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Division of Agriculture, University of Arkansas, Fayetteville, AR 72702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2653-0336","authenticated-orcid":false,"given":"Zully E.","family":"Contreras-Correa","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Tarleton State University, Stephenville, TX 76402, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hala","family":"El Daous","sequence":"additional","affiliation":[{"name":"Department of Animal and Dairy Sciences, Mississippi State University, Mississippi State, MS 39762, USA"},{"name":"Faculty of Veterinary Medicine, Benha University, Mushtuhur 13736, Qalyubia, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darcie","family":"Sidelinger","sequence":"additional","affiliation":[{"name":"Department of Pathobiology and Population Medicine, Mississippi State University College of Veterinary Medicine, Mississippi State, MS 39762, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heath","family":"King","sequence":"additional","affiliation":[{"name":"Department of Pathobiology and Population Medicine, Mississippi State University College of Veterinary Medicine, Mississippi State, MS 39762, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7207-3052","authenticated-orcid":false,"given":"Mark","family":"Arick","sequence":"additional","affiliation":[{"name":"Institute for Genomics, Biocomputing & Biotechnology, Mississippi State University, Mississippi State, MS 39762, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1377-0664","authenticated-orcid":false,"given":"Caleb","family":"Lemley","sequence":"additional","affiliation":[{"name":"Department of Animal and Dairy Sciences, Mississippi State University, Mississippi State, MS 39762, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.domaniend.2014.10.003","article-title":"Impact of Maternal Malnutrition during the Periconceptional Period on Mammalian Preimplantation Embryo Development","volume":"51","author":"Velazquez","year":"2015","journal-title":"Domest. 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