{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:31:53Z","timestamp":1792794713584,"version":"4.5.0"},"reference-count":87,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"de recherche du Quebec, Nature et technologie"},{"DOI":"10.13039\/501100000038","name":"National Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","award":["NSERC; RGPIN-2020-05726, RGPIN-2023-0523, and RGPIN-2019-04740"],"award-info":[{"award-number":["NSERC; RGPIN-2020-05726, RGPIN-2023-0523, and RGPIN-2019-04740"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"name":"R\u00e9seau Qu\u00e9becois en reproduction, Armand-Frappier scholarships and FRQS","id":[{"id":"https:\/\/ror.org\/03pf9d152","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In utero exposure to the synthetic estrogen diethylstilbestrol (DES) has been linked to developmental abnormalities and elevated breast cancer risk in adulthood in human and rodent models. Although the impact of DES on the mammary epithelium has been thoroughly investigated, its effect on the other cell types of the mammary gland remains understudied. Here, given that the mammary gland development is strongly associated with its microenvironment, we aimed to investigate how in utero DES exposure alters the mammary gland\u2019s stromal and immune function across key developmental stages. To achieve this aim, timed-pregnant rats were gavaged daily with DES or vehicle from gestation days 16 to 21, and female offspring mammary glands were analyzed at pre-puberty (postnatal day 21 [PND21]), puberty (PND46), and adulthood (PND90). We assessed morphological and extracellular matrix changes, performed transcriptomic cell-type enrichment analysis, measured cytokine expression, and quantified immune cell populations. DES-exposed mammary glands exhibited pronounced stromal remodeling, including increased collagen deposition and orientation by adulthood. Gene expression profiling indicated DES-induced stage-specific immune alterations: Immune cell signatures were enriched at PND21 and PND90 but diminished at PND46. Correspondingly, DES increased macrophage populations at PND21 while reducing T-lymphocyte numbers at PND46 and PND90. DES exposure also dysregulated inflammatory cytokine\/chemokine expression in adult glands, suggesting a persistent inflammatory environment. In conclusion, in utero exposure to an estrogenic compound can reprogram mammary development, inducing long-term changes in the extracellular matrix and immune landscape. These disruptions to stromal-immune homeostasis may impair normal mammary morphogenesis and increase susceptibility to breast pathologies later in life.<\/jats:p>","DOI":"10.1093\/toxsci\/kfaf157","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T13:04:16Z","timestamp":1762520656000},"source":"Crossref","is-referenced-by-count":1,"title":["An in utero exposure to the synthetic estrogen diethylstilbestrol affects the fat pad composition in post-natal mammary glands"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1005-4526","authenticated-orcid":false,"given":"David","family":"Tovar-Parra","sequence":"first","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS), Centre Armand-Frappier Sant\u00e9 Biotechnologie , Laval, QC H7V 1B7,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alec","family":"McDermott","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS), Centre Armand-Frappier Sant\u00e9 Biotechnologie , Laval, QC H7V 1B7,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jysiane","family":"Cardot","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS), Centre Armand-Frappier Sant\u00e9 Biotechnologie , Laval, QC H7V 1B7,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melany Nicole","family":"Juarez","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS), Centre Armand-Frappier Sant\u00e9 Biotechnologie , Laval, QC H7V 1B7,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Joao","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS), Centre Armand-Frappier Sant\u00e9 Biotechnologie , Laval, QC H7V 1B7,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhizlane","family":"El Omri-Charai","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS), Centre Armand-Frappier Sant\u00e9 Biotechnologie , Laval, QC H7V 1B7,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Line","family":"Berthiaume","sequence":"additional","affiliation":[{"name":"Axe Endocrinologie-N\u00e9phrologie, Centre de recherche du CHU de Qu\u00e9bec-Universit\u00e9 Laval , Quebec, QC G1V 4G2,","place":["Canada"]},{"name":"Centre de recherche en reproduction, d\u00e9veloppement et sant\u00e9 interg\u00e9n\u00e9rationnelle (CRDSI) de l\u2019Universit\u00e9 Laval , Quebec, QC G1V 4G2,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhawna","family":"Dhawan","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS) Centre \u00c9nergie Mat\u00e9riaux T\u00e9l\u00e9communications , Varennes, QC J3X 1P7,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arash","family":"Aghigh","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS) Centre \u00c9nergie Mat\u00e9riaux T\u00e9l\u00e9communications , Varennes, QC J3X 1P7,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yann","family":"Breton","sequence":"additional","affiliation":[{"name":"Axe Maladies infectieuses et immunitaires, Centre de recherche du CHU de Qu\u00e9bec-Universit\u00e9 Laval , Quebec, QC G1V 4G2,","place":["Canada"]},{"name":"Arthritis Research Center, Laval University , Quebec, QC G1V 4G2,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"L\u00e9gar\u00e9","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS) Centre \u00c9nergie Mat\u00e9riaux T\u00e9l\u00e9communications , Varennes, QC J3X 1P7,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9169-1075","authenticated-orcid":false,"given":"G\u00e9raldine","family":"Delb\u00e8s","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS), Centre Armand-Frappier Sant\u00e9 Biotechnologie , Laval, QC H7V 1B7,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5033-4947","authenticated-orcid":false,"given":"Martin","family":"Pelletier","sequence":"additional","affiliation":[{"name":"Axe Maladies infectieuses et immunitaires, Centre de recherche du CHU de Qu\u00e9bec-Universit\u00e9 Laval , Quebec, QC G1V 4G2,","place":["Canada"]},{"name":"Arthritis Research Center, Laval University , Quebec, QC G1V 4G2,","place":["Canada"]},{"name":"Department of Microbiology-Infectious Diseases and Immunology, Faculty of Medicine, Universit\u00e9 Laval , Quebec, QC G1V 0A6,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9tienne","family":"Audet-Walsh","sequence":"additional","affiliation":[{"name":"Axe Endocrinologie-N\u00e9phrologie, Centre de recherche du CHU de Qu\u00e9bec-Universit\u00e9 Laval , Quebec, QC G1V 4G2,","place":["Canada"]},{"name":"Centre de recherche en reproduction, d\u00e9veloppement et sant\u00e9 interg\u00e9n\u00e9rationnelle (CRDSI) de l\u2019Universit\u00e9 Laval , Quebec, QC G1V 4G2,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2080-6450","authenticated-orcid":false,"given":"Isabelle","family":"Plante","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS), Centre Armand-Frappier Sant\u00e9 Biotechnologie , Laval, QC H7V 1B7,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,9]]},"reference":[{"key":"2026021910563996300_kfaf157-B1","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1001\/jama.1976.03270110011002","article-title":"Exposure in utero to diethylstilbestrol and related synthetic hormones. 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