{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:55:04Z","timestamp":1789786504735,"version":"4.0.1"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2010,6,1]],"date-time":"2010-06-01T00:00:00Z","timestamp":1275350400000},"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":[[2010,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We previously demonstrated that in the CD-1 mouse, which exhibits a high incidence of age-related adenomyosis, neonatal exposure to tamoxifen induced premature uterine adenomyosis and was associated with abnormal development particularly of the inner myometrium. In the present study, we examined the effect of neonatal tamoxifen administration upon uterine development in the C57\/BL6J mouse strain that is not known to develop uterine adenomyosis. Female C57\/BL6J pups (n=20) were treated with oral tamoxifen (1\u200amg\/kg) from age 1 to 5 days. Uteri from control and treated mice were obtained on days 5, 10, 15 and 42 of age. We examined sections histologically using image analysis and immunohistochemistry for \u03b1-smooth muscle actin (ACTA2, \u03b1-SMA), desmin, vimentin, laminin, fibronectin and oestrogen receptor-\u03b1 (ESR1). Following tamoxifen exposure, all uteri showed inner myometrium thinning, lack of continuity, disorganisation and bundling. However, adenomyosis was not seen in any uterus. ACTA2 immunostaining was less in the circular muscle layer of treated mice. The temporal pattern of desmin immunostaining found in control mice was absent in tamoxifen-treated mice. There was no difference in the localisation of laminin or fibronectin between control and tamoxifen-treated groups. However, laminin immunostaining was reduced in the circular muscle layer of treated mice. Vimentin could not be detected in either group. In conclusion, our results demonstrate that the development of the inner myometrium is particularly sensitive to oestrogen antagonism, and is affected by steroid receptor modulation. Although tamoxifen induces inner myometrial changes including that of ACTA2, desmin, ESR1 and laminin expression in C57\/BL6J neonatal mice similar to those induced in CD-1 mice, C57\/BL6J mice did not develop premature adenomyosis. Thus, disruption of the development and differentiation of the inner myometrium cannot alone explain the development of tamoxifen-associated adenomyosis, and this must be dependent upon its interaction with strain-dependent factors.<\/jats:p>","DOI":"10.1530\/rep-09-0443","type":"journal-article","created":{"date-parts":[[2010,3,16]],"date-time":"2010-03-16T21:00:48Z","timestamp":1268773248000},"page":"1067-1075","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":25,"title":["Neonatal administration of tamoxifen causes disruption of myometrial development but not adenomyosis in the C57\/BL6J mouse"],"prefix":"10.1093","volume":"139","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":[[2010,6,1]]},"reference":[{"key":"2026010712515069500_bib1","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1007\/BF02897237","article-title":"Interaction of antiestrogens with binding sites for muscarinic cholinergic drugs and calcium channel blockers in cell membranes","volume":"26","author":"Batra","year":"1990","journal-title":"Cancer Chemotherapy and Pharmacology"},{"key":"2026010712515069500_bib2","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1210\/endo-126-5-2592","article-title":"Strain differences in the ontogeny of estrogen receptors in murine uterine epithelium","volume":"126","author":"Bigsby","year":"1990","journal-title":"Endocrinology"},{"key":"2026010712515069500_bib3","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/0002-9378(72)90781-8","article-title":"The elusive adenomyosis of the uterus \u2013 revisited","volume":"112","author":"Bird","year":"1972","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"2026010712515069500_bib4","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":"2026010712515069500_bib5","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":"2026010712515069500_bib6","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":"2026010712515069500_bib7","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1067\/mob.2002.124285","article-title":"Disruption of the endometrial\u2013myometrial border during pregnancy as a risk factor for adenomyosis","volume":"187","author":"Curtis","year":"2002","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"2026010712515069500_bib8","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":"2026010712515069500_bib9","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":"2026010712515069500_bib10","first-page":"249","article-title":"Adenomyosis in mice","volume":"22","author":"Guttner","year":"1980","journal-title":"Zeitschrift f\u00fcr Versuchstierkunde"},{"key":"2026010712515069500_bib11","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":"2026010712515069500_bib12","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/0002-9378(82)90189-2","article-title":"Effects of prenatal exposure of mice to \u201clow-dose\u201d 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":"2026010712515069500_bib13","first-page":"402","article-title":"Endocrine disruption and developmental abnormalities of female reproduction","volume":"40","author":"Iguchi","year":"2000","journal-title":"American Zoologist"},{"key":"2026010712515069500_bib14","first-page":"175","article-title":"Critical period of induction by tamoxifen of genital organ abnormalities in female mice","volume":"4","author":"Irisawa","year":"1990","journal-title":"In Vivo"},{"key":"2026010712515069500_bib15","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":"2026010712515069500_bib16","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":"2026010712515069500_bib17","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":"2026010712515069500_bib18","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":"2026010712515069500_bib19","first-page":"688","article-title":"Adenomyosis: symptoms, histology, and pregnancy terminations","volume":"95","author":"Levgur","year":"2000","journal-title":"Obstetrics and Gynecology"},{"key":"2026010712515069500_bib20","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/BF00268912","article-title":"Relationship between cellular DNA synthesis. PCNA expression and sex steroid hormone receptor status in the developing mouse ovary, uterus and oviduct","volume":"102","author":"Li","year":"1994","journal-title":"Histochemistry"},{"key":"2026010712515069500_bib21","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":"2026010712515069500_bib22","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":"2026010712515069500_bib23","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1530\/REP-09-0054","article-title":"The effects of tamoxifen and estradiol on myometrial differentiation and organization during early uterine development in the CD1 mouse","volume":"138","author":"Mehasseb","year":"2009","journal-title":"Reproduction"},{"key":"2026010712515069500_bib24","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":"2026010712515069500_bib25","first-page":"40","article-title":"Strain-difference in the induction of adenomyosis by intrauterine pituitary grafting in mice","volume":"32","author":"Mori","year":"1982","journal-title":"Laboratory Animal Science"},{"key":"2026010712515069500_bib26","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":"2026010712515069500_bib27","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":"2026010712515069500_bib28","first-page":"3985","article-title":"A matrix metalloproteinase inhibitor, ONO-4817, retards the development of mammary tumor and the progression of uterine adenomyosis in mice","volume":"22","author":"Mori","year":"2002","journal-title":"Anticancer Research"},{"key":"2026010712515069500_bib29","first-page":"345","article-title":"Relationship between incidence and onset age of mammary tumours and uterine adenomyosis in four strains of mice: comparison with the findings of 40 generations previously","volume":"15","author":"Nagasawa","year":"2001","journal-title":"In Vivo"},{"key":"2026010712515069500_bib30","first-page":"237","article-title":"Relationship between mammary tumourigenesis and uterine adenomyosis in four strains of mice","volume":"1","author":"Nagasawa","year":"1987","journal-title":"In Vivo"},{"key":"2026010712515069500_bib31","first-page":"827","article-title":"Stimulation of mammary tumourigenesis and inhibition of uterine adenomyosis by suppressed progesterone effects in SHN mice","volume":"9","author":"Nagasawa","year":"1989","journal-title":"Anticancer Research"},{"key":"2026010712515069500_bib32","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":"2026010712515069500_bib33","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":"2026010712515069500_bib34","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":"2026010712515069500_bib35","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 and Cell Biology"},{"key":"2026010712515069500_bib36","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":"2026010712515069500_bib37","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":"2026010712515069500_bib38"},{"key":"2026010712515069500_bib39","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\/139\/6\/1067.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/reproduction\/article-pdf\/139\/6\/1067\/64532240\/1067.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/reproduction\/article-pdf\/139\/6\/1067\/64532240\/1067.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T17:55:42Z","timestamp":1767808542000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/reproduction\/article\/139\/6\/1067\/8243162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,1]]},"references-count":39,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2010,6,1]]}},"URL":"https:\/\/doi.org\/10.1530\/rep-09-0443","relation":{},"ISSN":["1470-1626","1741-7899"],"issn-type":[{"value":"1470-1626","type":"print"},{"value":"1741-7899","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2010,6,1]]},"published":{"date-parts":[[2010,6,1]]}}}