{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T21:24:10Z","timestamp":1787693050950,"version":"build-2784847793"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Genome Canada and Genome Quebec"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Infertility and post-partum reproductive diseases are significant challenges in cattle farming, with the maternal immune system\u2019s ability to recognize and tolerate the embryo being crucial for successful gestation. DNA methylation in hematopoietic cells may influence susceptibility to post-partum fertility issues, making the identification of epigenetic changes vital for sustainable animal production. This study aimed to characterize the methylome of immune cells in relation to fertility, potentially enabling early detection of subfertility. Using whole epigenome sequencing and enzymatic methyl-seq, we analyzed DNA methylation patterns in blood from twelve Holstein cows before the onset of any disease. Our findings revealed 216 990 differentially methylated cytosines (DMCs) between fertile and subfertile cows. Notably, three genes\u2014Interferon tau-3 (IFNT3), KIAA0825, and RAS-Related Protein 2A\u2014showed high significance in their differential methylation between fertile and subfertile cows. IFNT3, crucial for early embryonic development, had seven DMCs in its transcription start site (TSS) shores in subfertile cows. Additionally, the KLRA1 gene (Ly49), was identified as containing DMCs across all five genomic regions analyzed (TSS shores, exons, introns, downstream, and distal intergenic). Its widespread differential methylation highlights its potential impact on fertility. Key interleukin genes, including IL6, IL15, IL22, and IL36G, also showed multiple DMCs, reinforcing the role of the immune system in bovine fertility. These findings illustrate the potential control that immune cell epigenetics exert on cattle post-partum fertility. Additionally, this study suggests that the risk of developing subfertility could potentially be estimated with as few as 220 biomarkers, paving the way for enhanced animal health management and improved fertility treatments.<\/jats:p>","DOI":"10.1093\/biolre\/ioaf020","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T13:26:50Z","timestamp":1738762010000},"page":"388-402","source":"Crossref","is-referenced-by-count":6,"title":["Epigenetic insights into fertility: involvement of immune cell methylation in dairy cows reproduction"],"prefix":"10.1093","volume":"115","author":[{"given":"Lotfi","family":"Bouzeraa","sequence":"first","affiliation":[{"name":"Department of Animal Sciences, Faculty of Agricultural and Food Sciences, Laval University , Qu\u00e9bec, QC ,","place":["Canada"]},{"name":"Research Center in Reproduction, Development, and Intergenerational Health (CRDSI) , Qu\u00e9bec, QC ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, Faculty of Agricultural and Food Sciences, Laval University , Qu\u00e9bec, QC ,","place":["Canada"]},{"name":"Research Center in Reproduction, Development, and Intergenerational Health (CRDSI) , Qu\u00e9bec, QC ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Dufour","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Faculty of Medicine, Laval University , Qu\u00e9bec, QC ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica C S","family":"Marques","sequence":"additional","affiliation":[{"name":"Faculty of Land and Food Systems, University of British Columbia , Vancouver, BC ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronaldo","family":"Cerri","sequence":"additional","affiliation":[{"name":"Faculty of Land and Food Systems, University of British Columbia , Vancouver, BC ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc-Andre","family":"Sirard","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, Faculty of Agricultural and Food Sciences, Laval University , Qu\u00e9bec, QC ,","place":["Canada"]},{"name":"Research Center in Reproduction, Development, and Intergenerational Health (CRDSI) , Qu\u00e9bec, QC ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"2026081805380931900_ref1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S1472-6483(10)62187-6","article-title":"Definition and causes of infertility","volume":"2","author":"Brugo-Olmedo","year":"2001","journal-title":"Reprod Biomed Online"},{"key":"2026081805380931900_ref2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.theriogenology.2016.04.037","article-title":"Pivotal periods for pregnancy loss during the first trimester of gestation in lactating dairy cows","volume":"86","author":"Wiltbank","year":"2016","journal-title":"Theriogenology"},{"key":"2026081805380931900_ref3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.theriogenology.2020.01.041","article-title":"Breeding animals to feed people: the many roles of animal reproduction in ensuring global food security","volume":"150","author":"Davis","year":"2020","journal-title":"Theriogenology"},{"key":"2026081805380931900_ref4","doi-asserted-by":"crossref","first-page":"4486","DOI":"10.2527\/jas.2013-6465","article-title":"Heifer calving date positively influences calf weaning weights through six parturitions","volume":"91","author":"Cushman","year":"2013","journal-title":"J Anim Sci"},{"key":"2026081805380931900_ref5","doi-asserted-by":"crossref","first-page":"12664","DOI":"10.1038\/s41598-023-39858-0","article-title":"A multi-omics analysis identifies molecular features associated with fertility in heifers (Bos taurus)","volume":"13","author":"Marrella","year":"2023","journal-title":"Sci Rep"},{"key":"2026081805380931900_ref6","doi-asserted-by":"crossref","first-page":"423","DOI":"10.22358\/jafs\/67036\/2005","article-title":"Fertility measures in polish black-and-White cattle. 1. 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