{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:44:19Z","timestamp":1760143459186,"version":"build-2065373602"},"reference-count":81,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CNRS"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim of this study was to assess the long-term effect of exposure to environmentally relevant doses of non-steroidal anti-inflammatory drugs (NSAIDs; ibuprofen, and diclofenac) and 17\u03b2-ethinylestradiol (EE2) on the mouse uterus. NSAID-EE2 mixtures were administered in the drinking water from gestational day 8 until 8 weeks post-birth (i.e., during embryo development, lactation, puberty, and sexual maturity). The incidence of adenomyosis lesions (presence of endometrial glands in the inner myometrium) increased up to 60% in the uterus of 8-week-old exposed females (F1) and to 85% in F2 females (exposed father). Histological analysis revealed aberrant proliferation and apoptosis, vacuolization of epithelial cells, and increased incidence of abnormal glands in the luminal and glandular epithelium in F1 and F2 uteri. Moreover, myofibroblast proportion (alpha-smooth muscle actin (\u03b1-SMA) expression analysis) and collagen expression (Picrosirius red stain; a fibrosis hallmark) were increased in F1 and F2 endometrium. Connexin-43 was aberrantly distributed in the endometrial stroma and glands of F1 and F2 uteri. Conversely, uterine 17\u03b2-estradiol and progesterone levels were not affected in F1 and F2 females. These findings demonstrated that in mice, chronic exposure to NSAID and EE2 mixtures at environmental doses intergenerationally affects uterine physiology, particularly the endometrium. It may serve as a model to study the pathophysiology of human adenomyosis.<\/jats:p>","DOI":"10.3390\/ijms25042003","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T03:47:09Z","timestamp":1707277629000},"page":"2003","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Adenomyotic Lesions Are Induced in the Mouse Uterus after Exposure to NSAID and EE2 Mixtures at Environmental Doses"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2333-1745","authenticated-orcid":false,"given":"Brigitte","family":"Boizet-Bonhoure","sequence":"first","affiliation":[{"name":"D\u00e9veloppement et Pathologie de la Gonade, Institut de G\u00e9n\u00e9tique Humaine, Centre National de la Recherche Scientifique, Universit\u00e9 de Montpellier UMR9002, 34090 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5328-1414","authenticated-orcid":false,"given":"St\u00e9phanie","family":"D\u00e9jardin","sequence":"additional","affiliation":[{"name":"D\u00e9veloppement et Pathologie de la Gonade, Institut de G\u00e9n\u00e9tique Humaine, Centre National de la Recherche Scientifique, Universit\u00e9 de Montpellier UMR9002, 34090 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e9lissa","family":"Girard","sequence":"additional","affiliation":[{"name":"D\u00e9veloppement et Pathologie de la Gonade, Institut de G\u00e9n\u00e9tique Humaine, Centre National de la Recherche Scientifique, Universit\u00e9 de Montpellier UMR9002, 34090 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quentin","family":"Durix","sequence":"additional","affiliation":[{"name":"IExplore-RAM, Institut de G\u00e9nomique Fonctionnelle, Centre National de la Recherche Scientifique, INSERM, Universit\u00e9 de Montpellier, 34090 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis","family":"Poulat","sequence":"additional","affiliation":[{"name":"D\u00e9veloppement et Pathologie de la Gonade, Institut de G\u00e9n\u00e9tique Humaine, Centre National de la Recherche Scientifique, Universit\u00e9 de Montpellier UMR9002, 34090 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6384-521X","authenticated-orcid":false,"given":"Pascal","family":"Philibert","sequence":"additional","affiliation":[{"name":"D\u00e9veloppement et Pathologie de la Gonade, Institut de G\u00e9n\u00e9tique Humaine, Centre National de la Recherche Scientifique, Universit\u00e9 de Montpellier UMR9002, 34090 Montpellier, France"},{"name":"Laboratoire de Biochimie et Biologie Mol\u00e9culaire, H\u00f4pital Car\u00e9meau, CHU de N\u00eemes, 30029 N\u00eemes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.rbmo.2011.10.003","article-title":"Adenomyosis and infertility","volume":"24","author":"Campo","year":"2012","journal-title":"Reprod. 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