{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T19:21:58Z","timestamp":1783797718146,"version":"3.55.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2009,8,1]],"date-time":"2009-08-01T00:00:00Z","timestamp":1249084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["rep.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We used a neonatal mouse model to examine the histogenesis of uterine adenomyosis, and to test whether adenomyosis is due to an abnormality in myometrial differentiation, or in extracellular matrix proteins expression. We also studied the effects of tamoxifen and estradiol on uterine development, myometrial differentiation, and organization. Female CD1 pups were treated with oral tamoxifen (1\u200amg\/kg) (n=27) or estradiol (0.1\u200amg\/kg) (n=24) from age 1 to 5 days. Uteri from control (n=27) and treated mice were obtained on days 2, 5, 10, 15, and 42 of age. We examined the sections histologically, using image analysis and immunohistochemistry for \u03b1-smooth muscle actin (\u03b1-SMA), desmin, vimentin, laminin, fibronectin, and estrogen receptor-\u03b1. Following tamoxifen exposure, all uteri showed adenomyosis by 6 weeks of age (seen as early as day 10). The inner myometrium showed thinning, lack of continuity, disorganization, and bundling. \u03b1-SMA expression was normal. Desmin expression normally showed a wave of maturation that was absent in tamoxifen-treated mice. In the estradiol group, adenomyosis was not observed. All uterine layers were normally developed, but hypertrophied. The inner myometrium retained its circular arrangement. There was no difference in the localization of laminin or fibronectin between groups (laminin expression was reduced in the tamoxifen treated uteri). Vimentin could not be detected in all groups. Our results suggest that the development of the inner myometrium is particularly sensitive to estrogen antagonism, and can be affected by steroid receptors modulation. Disruption of the inner myometrium may play a role in the development of uterine adenomyosis.<\/jats:p>","DOI":"10.1530\/rep-09-0054","type":"journal-article","created":{"date-parts":[[2009,5,18]],"date-time":"2009-05-18T20:55:14Z","timestamp":1242680114000},"page":"341-350","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":50,"title":["The effects of tamoxifen and estradiol on myometrial differentiation and organization during early uterine development in the CD1 mouse"],"prefix":"10.1093","volume":"138","author":[{"given":"Mohamed K","family":"Mehasseb","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S C","family":"Bell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M A","family":"Habiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,8,1]]},"reference":[{"key":"2026010712510311400_bib1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0889-8545(21)00148-0","article-title":"Adenomyosis: current perspectives","volume":"16","author":"Azziz","year":"1989","journal-title":"Obstetrics and Gynecology Clinics of North America"},{"key":"2026010712510311400_bib2","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1354\/vp.39-5-572","article-title":"Endometrial hyperplasia, polyps, and adenomyosis associated with unopposed estrogen in rhesus monkeys (Macaca mulatta)","volume":"39","author":"Baskin","year":"2002","journal-title":"Veterinary Pathology"},{"key":"2026010712510311400_bib3","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1007\/BF02897237","article-title":"Interaction of antiestrogens with binding sites for muscarinic cholinergic drugs and clacium channel blockers in cell membranes","volume":"26","author":"Batra","year":"1990","journal-title":"Cancer Chemotherapy and Pharmacology"},{"key":"2026010712510311400_bib4","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/0002-9378(72)90781-8","article-title":"The elusive adenomyosis of the uterus-revisited","volume":"112","author":"Bird","year":"1972","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"2026010712510311400_bib5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/aja.1001860102","article-title":"Histologic, morphometric, and immunocytochemical analysis of myometrial development in rats and mice: I. Normal development","volume":"186","author":"Brody","year":"1989","journal-title":"American Journal of Anatomy"},{"key":"2026010712510311400_bib6","doi-asserted-by":"crossref","first-page":"6909","DOI":"10.1073\/pnas.81.22.6909","article-title":"Characterization and regulation in the expression of a gene encoding for the intermediate filament protein desmin","volume":"81","author":"Capetanaki","year":"1984","journal-title":"PNAS"},{"key":"2026010712510311400_bib7","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1002\/jez.1401960310","article-title":"Stromal induction and specification of morphogenesis and cytodifferentiation of the epithelia of the mullerian ducts and urogenital sinus during development of the uterus and vagina in mice","volume":"196","author":"Cunha","year":"1976","journal-title":"Journal of Experimental Zoology"},{"key":"2026010712510311400_bib8","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1095\/biolreprod40.4.861","article-title":"Role of uterine epithelium in the development of myometrial smooth muscle cells","volume":"40","author":"Cunha","year":"1989","journal-title":"Biology of Reproduction"},{"key":"2026010712510311400_bib9","first-page":"76","article-title":"Role of epithelial\u2013mesenchymal interactions in the differentiation and spatial organization of visceral smooth muscle","volume":"1","author":"Cunha","year":"1992","journal-title":"Epithelial Cell Biology"},{"key":"2026010712510311400_bib10","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/BF00225113","article-title":"The effect of oestradiol on the DNA synthesis in neonatal mouse uterus and cervix","volume":"156","author":"Eide","year":"1975","journal-title":"Cell Tissue Research"},{"key":"2026010712510311400_bib11","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.bpobgyn.2006.01.003","article-title":"Experimental adenomyosis","volume":"20","author":"Greaves","year":"2006","journal-title":"Best Practice & Research. Clinical Obstetrics & Gynaecology"},{"key":"2026010712510311400_bib12","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1677\/joe.0.1700555","article-title":"Comparisons of the effects of tamoxifen, toremifene and raloxifene on enzyme induction and gene expression in the ovariectomised rat uterus","volume":"170","author":"Green","year":"2001","journal-title":"Journal of Endocrinology"},{"key":"2026010712510311400_bib13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1677\/jme.0.0300001","article-title":"Comparison of the effect of oestradiol, tamoxifen and raloxifene on nerve growth factor-alpha expression in specific neonatal mouse uterine cell types using laser capture microdissection","volume":"30","author":"Green","year":"2003","journal-title":"Journal of Molecular Endocrinology"},{"key":"2026010712510311400_bib14","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.etp.2004.10.001","article-title":"Neonatal tamoxifen treatment of mice leads to adenomyosis but not uterine cancer","volume":"56","author":"Green","year":"2005","journal-title":"Experimental and Toxicologic Pathology"},{"key":"2026010712510311400_bib15","first-page":"249","article-title":"Adenomyosis in mice","volume":"22","author":"Guttner","year":"1980","journal-title":"Zeitschrift f\u00fcr Versuchstierkunde"},{"key":"2026010712510311400_bib16","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/aja.1001770211","article-title":"The ontogeny of the mouse estrogen receptor: the pelvic region","volume":"177","author":"Holderegger","year":"1986","journal-title":"American Journal of Anatomy"},{"key":"2026010712510311400_bib17","doi-asserted-by":"crossref","first-page":"4463","DOI":"10.1016\/0006-2952(86)90764-1","article-title":"Inhibition of protein kinase C mediated signal transduction by tamoxifen","volume":"35","author":"Horgan","year":"1986","journal-title":"Biochemical Pharmacology"},{"key":"2026010712510311400_bib18","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/0002-9378(82)90189-2","article-title":"Effects of prenatal exposure of mice to \u2018low-dose\u2019 diethylstilbestrol and the development of adenomyosis associated with evidence of hyperprolactinemia","volume":"144","author":"Huseby","year":"1982","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"2026010712510311400_bib19","first-page":"402","article-title":"Endocrine disruption and developmental abnormalities of female reproduction","volume":"40","author":"Iguchi","year":"2000","journal-title":"American Zoologist"},{"key":"2026010712510311400_bib20","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1095\/biolreprod62.2.310","article-title":"Expression of estrogen receptor beta is developmentally regulated in reproductive tissues of male and female mice","volume":"62","author":"Jefferson","year":"2000","journal-title":"Biology of Reproduction"},{"key":"2026010712510311400_bib21","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1126\/science.7985022","article-title":"Insights from the study of animals lacking functional estrogen receptor","volume":"266","author":"Korach","year":"1994","journal-title":"Science"},{"key":"2026010712510311400_bib22","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S0002-9378(97)70503-9","article-title":"Potent inhibition by tamoxifen of spontaneous and agonist-induced contractions of the human myometrium and intramyometrial arteries","volume":"176","author":"Kostrzewska","year":"1997","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"2026010712510311400_bib23","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/0006-291X(85)91302-6","article-title":"Evidence tat tamoxifen is a histamine antagonist","volume":"131","author":"Kroeger","year":"1985","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"2026010712510311400_bib24","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1006\/dbio.2001.0458","article-title":"Epithelial\u2013stromal tissue interaction in paramesonephric (Mullerian) epithelial differentiation","volume":"240","author":"Kurita","year":"2001","journal-title":"Developmental Biology"},{"key":"2026010712510311400_bib25","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0006-291X(84)91062-3","article-title":"Tamoxifen is a calmodulin antagonist in the activation of cAMP phosphodiesterase","volume":"118","author":"Lam","year":"1984","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"2026010712510311400_bib26","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/283249a0","article-title":"Intermediate filaments as mechanical integrators of cellular space","volume":"238","author":"Lazarides","year":"1980","journal-title":"Nature"},{"key":"2026010712510311400_bib27","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1083\/jcb.139.1.129","article-title":"Desmin is essential for the tensile strength and integrity of myofibrls but not for myogenic commitment, differentiation, and fusion of skeletal muscle","volume":"139","author":"Li","year":"1997","journal-title":"Journal of Cell Biology"},{"key":"2026010712510311400_bib28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cm.970290102","article-title":"Sequential appearance of muscle-specific proteins in myoblasts as a function of time after cell division: evidence for a conserved myoblast differentiation program in skeletal muscle","volume":"29","author":"Lin","year":"1994","journal-title":"Cell Motility and the Cytoskeleton"},{"key":"2026010712510311400_bib29","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/bjc.1967.15","article-title":"Pathological changes induced in the uterus of mice with the prolonged administration of progesterone and 19-nor-contraceptives","volume":"21","author":"Lipschutz","year":"1967","journal-title":"British Journal of Cancer"},{"key":"2026010712510311400_bib30","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/BF00253056","article-title":"Calcium antagonism by the antioestrogen tamoxifen","volume":"18","author":"Lipton","year":"1986","journal-title":"Cancer Chemotherapy and Pharmacology"},{"key":"2026010712510311400_bib31","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1677\/joe.0.0560133","article-title":"Hypertrophy and hyperplasia in the mouse uterus after oestrogen treatment: an autoradiographic study","volume":"56","author":"Martin","year":"1973","journal-title":"Journal of Endocrinology"},{"key":"2026010712510311400_bib32","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1067\/mob.2001.117967","article-title":"Increased invasion activity of endometrial stromal cells and elevated expression of matrix metalloproteinase messenger RNA in the uterine tissues of mice with experimentally induced adenomyosis","volume":"185","author":"Matsuda","year":"2001","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"2026010712510311400_bib33","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/0002-9378(70)90034-7","article-title":"Endometriosis in rhesus monkeys","volume":"106","author":"McCann","year":"1970","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"2026010712510311400_bib34","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1083\/jcb.134.5.1255","article-title":"Disruption of muscle architecture and myocardial degeneration in mice lacking desmin","volume":"134","author":"Milner","year":"1996","journal-title":"Journal of Cell Biology"},{"key":"2026010712510311400_bib35","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1289\/ehp.7028","article-title":"The need to decide if all estrogens are intrinsically similar","volume":"112","author":"Moggs","year":"2004","journal-title":"Environmental Health Perspectives"},{"key":"2026010712510311400_bib36","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1159\/000145724","article-title":"Mechanisms of development of prolactin-induced adenomyosis in mice","volume":"116","author":"Mori","year":"1983","journal-title":"Acta Anatomica"},{"key":"2026010712510311400_bib37","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/0024-3205(81)90234-4","article-title":"The induction of adenomyosis in mice by intrauterine pituitary isografts","volume":"29","author":"Mori","year":"1981","journal-title":"Life Sciences"},{"key":"2026010712510311400_bib38","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1007\/BF01951902","article-title":"Ultrastructural changes in uterine myometrium of mice with experimentally-induced adenomyosis","volume":"40","author":"Mori","year":"1984","journal-title":"Experientia"},{"key":"2026010712510311400_bib39","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/0002-9378(91)90258-S","article-title":"Animal model of uterine adenomyosis: is prolactin a potent inducer of adenomyosis in mice?","volume":"165","author":"Mori","year":"1991","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"2026010712510311400_bib40","first-page":"239","article-title":"Ultrastructural changes of endometrium and myometrium during development of adenomyosis in mice with ectopic pituitary transplants","volume":"2","author":"Ohta","year":"1985","journal-title":"Zoological Science"},{"key":"2026010712510311400_bib41","first-page":"121","article-title":"Long-term responses of the mouse uterus to neonatal diethylstilbestrol treatment and to later sex hormone exposure","volume":"74","author":"Ostrander","year":"1985","journal-title":"Journal of the National Cancer Institute"},{"key":"2026010712510311400_bib42","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1034\/j.1399-0004.2000.570604.x","article-title":"Sporadic cardiac and skeletal myopathy caused by a de nove desmin mutation","volume":"57","author":"Park","year":"2000","journal-title":"Clinical Genetics"},{"key":"2026010712510311400_bib43","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/S0002-9440(10)61733-6","article-title":"Adenomyosis \u2013 a result of disordered stromal differentiation","volume":"159","author":"Parrott","year":"2001","journal-title":"American Journal of Pathology"},{"key":"2026010712510311400_bib44","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/S1357-2725(96)00172-0","article-title":"Fibronectin","volume":"29","author":"Romberger","year":"1997","journal-title":"International Journal of Biochemistry & Cell Biology"},{"key":"2026010712510311400_bib45","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/modpathol.3800574","article-title":"Estrogen receptor-beta is expressed in stromal cells of fibroadenoma and phyllodes tumors of the breast","volume":"19","author":"Sapino","year":"2006","journal-title":"Modern Pathology"},{"key":"2026010712510311400_bib46","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1083\/jcb.200401058","article-title":"Laminin: the crux of basement membranes assembly","volume":"164","author":"Sasaki","year":"2004","journal-title":"Journal of Cell Biology"},{"key":"2026010712510311400_bib47","first-page":"151","article-title":"Estrogen receptor expressin in genital tract of female mice treated neonatally with diethylstilbestrol","volume":"6","author":"Sato","year":"1992","journal-title":"In Vivo"},{"key":"2026010712510311400_bib48","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1016\/S0006-3495(04)74349-0","article-title":"Structural and functional roles of desmin in mouse skeletal muscle during passive deformation","volume":"86","author":"Shah","year":"2004","journal-title":"Biophysical Journal"},{"key":"2026010712510311400_bib49","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-4731(80)90250-2","article-title":"Estrogen receptors in the fetal mouse","volume":"12","author":"Stumpf","year":"1980","journal-title":"Journal of Steroid Biochemistry"},{"key":"2026010712510311400_bib50"},{"key":"2026010712510311400_bib51","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.1210\/endo-125-6-2888","article-title":"Developmental pattern of estrogen receptor expression in female mouse genital tracts","volume":"125","author":"Yamashita","year":"1989","journal-title":"Endocrinology"}],"container-title":["Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rep.bioscientifica.com\/view\/journals\/rep\/138\/2\/341.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/reproduction\/article-pdf\/138\/2\/341\/64530397\/341.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/reproduction\/article-pdf\/138\/2\/341\/64530397\/341.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T17:54:28Z","timestamp":1767808468000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/reproduction\/article\/138\/2\/341\/8243117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,8,1]]},"references-count":51,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2009,8,1]]}},"URL":"https:\/\/doi.org\/10.1530\/rep-09-0054","relation":{},"ISSN":["1470-1626","1741-7899"],"issn-type":[{"value":"1470-1626","type":"print"},{"value":"1741-7899","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2009,8,1]]},"published":{"date-parts":[[2009,8,1]]}}}