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Emerging evidence indicates that epigenetic regulators, including histone modifications, play critical roles in uterine receptivity, implantation, and stromal cell decidualization. Our previous study demonstrated that loss of histone deacetylase 3 (HDAC3) impairs endometrial receptivity and decidualization, resulting in female infertility. However, the genome\u2010wide transcriptomic alterations responsible for defective decidualization in loss of HDAC3 remain unclear. In this study, uterine\u2010specific\n                    <jats:italic>Hdac3<\/jats:italic>\n                    knockout (\n                    <jats:italic>Pgr<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>cre\/+<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>Hdac3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>f\/f<\/jats:italic>\n                    <\/jats:sup>\n                    ;\n                    <jats:italic>Hdac3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>d\/d<\/jats:italic>\n                    <\/jats:sup>\n                    ) mice exhibited decidual defects following 3\u2009days of artificial decidualization. RNA sequencing analysis of uteri from control and\n                    <jats:italic>Hdac3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>d\/d<\/jats:italic>\n                    <\/jats:sup>\n                    mice revealed widespread dysregulation of genes and pathways associated with decidualization. Pathway analysis identified significant alterations in RHOA, AMPK\u2010NOTCH1\u2010HEY1, and oxidative stress\u2010induced senescence signaling, implicating dysregulation of cytoskeletal remodeling, cellular metabolism, and oxidative stress responses in the HDAC3\u2010mediated decidual response. Notably, expression of\n                    <jats:italic>Limk1<\/jats:italic>\n                    ,\n                    <jats:italic>Prkag1<\/jats:italic>\n                    , and\n                    <jats:italic>Cbx2<\/jats:italic>\n                    for key regulators of these pathways was significantly reduced in\n                    <jats:italic>Hdac3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>d\/d<\/jats:italic>\n                    <\/jats:sup>\n                    mice compared with controls. These findings demonstrate that HDAC3 is a key regulator of the transcriptional and signaling networks required for successful decidualization. Collectively, our study provides a comprehensive transcriptomic profile of HDAC3\u2010deficient uteri and uncovers key molecular mechanisms underlying impaired decidualization, thereby advancing our understanding of uterine function and pregnancy establishment.\n                  <\/jats:p>","DOI":"10.1096\/fj.202600629r","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T14:54:32Z","timestamp":1776264872000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["HDAC3 Regulates Transcriptional Networks Governing Decidualization"],"prefix":"10.1096","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3799-0514","authenticated-orcid":false,"given":"Loan Thi Kim","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Gynecology and Women's Health University of Missouri School of Medicine  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8278-1386","authenticated-orcid":false,"given":"Dinh Nam","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Women's Health University of Missouri School of Medicine  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0159-5558","authenticated-orcid":false,"given":"Shamsun","family":"Nahar","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Women's Health University of Missouri School of Medicine  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7823-5457","authenticated-orcid":false,"given":"Tae Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Women's Health University of Missouri School of Medicine  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