{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:03:57Z","timestamp":1782281037509,"version":"3.54.5"},"posted":{"date-parts":[[2025,11,15]]},"group-title":"Molecular Biology","reference-count":85,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T00:00:00Z","timestamp":1763164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"crossref","award":["ZIAES103311"],"award-info":[{"award-number":["ZIAES103311"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"crossref","award":["ZIAES103333"],"award-info":[{"award-number":["ZIAES103333"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"crossref","award":["NIEHS Intramural Opportunity Awards"],"award-info":[{"award-number":["NIEHS Intramural Opportunity Awards"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Identifying the factors that regulate female reproduction is crucial to understanding how the environment affects female reproductive health. The vitamin D receptor (VDR) and its ligands (primarily 1,25(OH)\n                  <jats:sub>2<\/jats:sub>\n                  D\n                  <jats:sub>3<\/jats:sub>\n                  ) have a recognized role in calcium homeostasis; however, their broader impact on female reproduction remains underexplored. We demonstrate that the VDR and its ligands are involved in the hormonal induction of uterine decidualization. Mice fed a vitamin D-deficient diet displayed an impaired hormonally induced decidual response. In a human telomerase reverse transcriptase-immortalized human endometrial stromal cell line (T-HESC), VDR decreased during in vitro decidualization. Small interfering RNA (siRNA) knockdown of VDR in T-HESC enhanced in vitro decidualization, while overexpression of VDR inhibited it. Chromatin accessibility and histone modification analyses revealed that VDR functions as a chromatin regulator, restricting accessibility and repressing transcription in specific genomic regions. Transcriptomic analyses confirmed that VDR broadly modulates gene expression, with most ligand-mediated effects occurring through the VDR. These findings identify VDR as a key regulator of transcriptional and chromatin landscapes in human endometrial stromal cells, offering novel insights into vitamin D signaling in reproduction. This study highlights the potential of targeting vitamin D pathways to treat uterine disorders associated with impaired decidualization and reduced fertility.\n                <\/jats:p>\n                <jats:sec id=\"s111\">\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" fig-type=\"figure\" orientation=\"portrait\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"688535v2_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2025.11.14.688535","type":"posted-content","created":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T03:55:11Z","timestamp":1763265311000},"source":"Crossref","is-referenced-by-count":0,"title":["Impact of vitamin D deficiency on defective endometrial decidualization and the repressive role of vitamin D receptor (VDR) in the epigenomic network"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6561-3620","authenticated-orcid":false,"given":"MyeongJin","family":"Yi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1418-8863","authenticated-orcid":false,"given":"Skylar G","family":"Montague Redecke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3970-0771","authenticated-orcid":false,"given":"Tianyuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1498-3012","authenticated-orcid":false,"given":"Austin","family":"Bell-Hensley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6172-784X","authenticated-orcid":false,"given":"Shuyun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1314-6650","authenticated-orcid":false,"given":"Abdull J.","family":"Massri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8635-9505","authenticated-orcid":false,"given":"Anne Marie Z.","family":"Jukic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9480-7336","authenticated-orcid":false,"given":"Francesco J.","family":"DeMayo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025112011551848000_2025.11.14.688535v2.1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2024-092901"},{"key":"2025112011551848000_2025.11.14.688535v2.2","doi-asserted-by":"crossref","unstructured":"T. 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