{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:52:39Z","timestamp":1790049159336,"version":"4.0.1"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":448,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T00:00:00Z","timestamp":1722556800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["rep.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,9,1]]},"abstract":"<jats:title>\u2003<\/jats:title>\n                  <jats:sec>\n                    <jats:title>In Brief<\/jats:title>\n                    <jats:p>Advanced maternal age is associated with a higher rate of pregnancy complications that are unrelated to karyotypic abnormalities of the oocyte. This study shows that the murine uterine stroma undergoes profound epigenetic changes affecting active and repressive histone modification profiles that are associated with impaired endometrial functionality and underpin the decline in reproductive performance of aged females.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Decidualization describes the transformation of the uterine stroma in response to an implanting embryo, a process critical for supporting the development of the early embryo, for ensuring normal placentation and ultimately for a healthy reproductive outcome. Maternal age has been found to impede the progression of decidualization, heightening the risk of reproductive problems. Here, we set out to comprehensively characterize this deficit by pursuing transcriptomic and epigenomic profiling approaches specifically in the uterine stromal cell (UtSC) compartment of young and aged female mice. We find that UtSCs from aged females are globally far less responsive to the decidualization stimulus triggered by exposure to the steroid hormones estrogen and progesterone. Despite an overall transcriptional hyperactivation of genes that are differentially expressed as a function of maternal age, the hormonally regulated genes specifically fail to be activated in aged UtSCs. Moreover, even in their unstimulated \u2018ground\u2019 state, UtSCs from aged females are epigenetically distinct, as determined by genomic enrichment profiling for the active and repressive histone marks H3K4me3 and H3K9me3, respectively. We find that many hormone-inducible genes exhibit a profound lack of promoter-associated H3K4me3 in aged UtSCs, implying that a significant enrichment of active histone marks prior to gene stimulation is required to enable the elicitation of a rapid transcriptional response. With this combination of criteria, our data highlight specific deficits in epigenetic marking and gene expression of ion channels and vascular markers. These results point to fundamental defects in muscle-related and perivascular niche functions of the uterine stroma with advanced maternal age.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/rep-24-0171","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T12:38:33Z","timestamp":1720787913000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":9,"title":["REPRODUCTIVE AGEING: Altered histone modification landscapes underpin defects in uterine stromal cell decidualization in aging females"],"prefix":"10.1093","volume":"168","author":[{"given":"Laura","family":"Woods","sequence":"first","affiliation":[{"name":"The Babraham Institute , Babraham Research Campus, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9441-5044","authenticated-orcid":false,"given":"Wendy","family":"Dean","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Anatomy , Cumming School of Medicine, Hospital Drive NW, University of Calgary, Calgary, Alberta, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute , University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3332-6958","authenticated-orcid":false,"given":"Myriam","family":"Hemberger","sequence":"additional","affiliation":[{"name":"Alberta Children\u2019s Hospital Research Institute , University of Calgary, Calgary, Alberta, Canada"},{"name":"Department of Biochemistry and Molecular Biology , Cumming School of Medicine, Hospital Drive NW, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,8,2]]},"reference":[{"key":"2026010712101604000_bib1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/978-3-319-15856-3_3","article-title":"The role of steroid hormone receptors in the establishment of pregnancy in rodents","volume":"216","author":"Adams","year":"2015","journal-title":"Advances in Anatomy, Embryology, and Cell Biology"},{"key":"2026010712101604000_bib2","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1002\/mrd.1142","article-title":"Control and expression of cystatin C by mouse decidual cultures","volume":"61","author":"Afonso","year":"2002","journal-title":"Molecular Reproduction and Development"},{"key":"2026010712101604000_bib3","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1038\/ncb1403","article-title":"Chromatin signatures of pluripotent cell lines","volume":"8","author":"Azuara","year":"2006","journal-title":"Nature Cell Biology"},{"key":"2026010712101604000_bib4","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1038\/nature04844","article-title":"Increased cell-to-cell variation in gene expression in ageing mouse heart","volume":"441","author":"Bahar","year":"2006","journal-title":"Nature"},{"key":"2026010712101604000_bib5","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/gm346","article-title":"H3K4me3 inversely correlates with DNA methylation at a large class of non-CpG-island-containing start sites","volume":"4","author":"Balasubramanian","year":"2012","journal-title":"Genome Medicine"},{"key":"2026010712101604000_bib6","doi-asserted-by":"publisher","first-page":"2687","DOI":"10.1242\/dev.122.9.2687","article-title":"Mechanisms of reduced fertility in Hoxa-10 mutant mice: uterine homeosis and loss of maternal Hoxa-10 expression","volume":"122","author":"Benson","year":"1996","journal-title":"Development"},{"key":"2026010712101604000_bib7","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.cell.2006.02.041","article-title":"A bivalent chromatin structure marks key developmental genes in embryonic stem cells","volume":"125","author":"Bernstein","year":"2006","journal-title":"Cell"},{"key":"2026010712101604000_bib8","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1530\/jrf.0.0030303","article-title":"Long-term reproductive performance of female mice. 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