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U.S.A."],"published-print":{"date-parts":[[2026,8,25]]},"abstract":"<jats:p>\n                    The developing female reproductive tract is highly sensitive to external hormonal stimulation, which can result in infertility and gynecologic diseases. To determine the underlying mechanisms, we used a mouse model to test the direct, cell type\u2013specific effects of neonatal exposure to the estrogenic chemical, diethylstilbestrol (DES), on the developing uterus. We found that control uterine epithelium is in a partial epithelial\u2013mesenchymal transition state that is lost following DES exposure. This is accompanied by evidence of premature differentiation including altered apical\u2013basal cell polarity and absence of the\n                    <jats:italic toggle=\"yes\">Lgr5<\/jats:italic>\n                    + epithelial stem cell population required for uterine gland formation. Cell\u2013cell communication between epithelial and mesenchymal cells is restructured, and Wnt signaling is aberrantly activated in the epithelium. The DES-exposed uterine mesenchyme has early signs of fibrosis through increased deposition of extracellular matrix (ECM) collagen. Mechanistically, DES exposure causes cell type\u2013specific changes in chromatin accessibility and gene expression, most prominently in epithelial cells. These changes can be explained in part by cell-specific alterations in chromatin looping at enhancer regions in concert with alterations in ER\u03b1 binding. These findings suggest that reprogramming cell type\u2013specific differentiation trajectories and ECM characteristics underlie the long-term phenotypic effects of developmental exposure to DES and possibly other estrogenic endocrine disrupting chemicals. These changes lead to functional impairment of adult tissues and increased cancer risk.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2603458123","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T19:03:46Z","timestamp":1786993426000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Neonatal diethylstilbestrol exposure disrupts uterine epithelial apical\u2013basal polarity and partial EMT state"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6014-2030","authenticated-orcid":false,"given":"Rachel E.","family":"Bainbridge","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}],"name":"Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, NIH","place":["Durham"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy N.","family":"Jefferson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}],"name":"Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, NIH","place":["Durham"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyuan","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}],"name":"Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH","place":["Durham"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3050-1909","authenticated-orcid":false,"given":"Sara A.","family":"Grimm","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}],"name":"Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH","place":["Durham"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6440-7086","authenticated-orcid":false,"given":"Carmen J.","family":"Williams","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}],"name":"Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, NIH","place":["Durham"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2016.07.011"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdrc.21035"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2153(05)68004-0"},{"key":"e_1_3_4_4_2","first-page":"40","article-title":"The development of the uterus in late fetal life, infancy, and childhood","volume":"14","author":"Valdes-Dapena M. 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