{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:47:00Z","timestamp":1791841620409,"version":"4.3.4"},"reference-count":30,"publisher":"The Company of Biologists","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,4,1]]},"abstract":"<jats:p>Women exposed to diethylstilbestrol (DES) in utero develop abnormalities,including cervicovaginal adenosis that can lead to cancer. We report that transient disruption of developmental signals by DES permanently changes expression of p63, thereby altering the developmental fate of Mu\u0308llerian duct epithelium. The cell fate of Mu\u0308llerian epithelium to be columnar(uterine) or squamous (cervicovaginal) is determined by mesenchymal induction during the perinatal period. Cervicovaginal mesenchyme induced p63 in Mu\u0308llerian duct epithelium and subsequent squamous differentiation. In p63\u2013\/\u2013 mice, cervicovaginal epithelium differentiated into uterine epithelium. Thus, p63 is an identity switch for Mu\u0308llerian duct epithelium to be cervicovaginal versus uterine. P63 was also essential for uterine squamous metaplasia induced by DES-exposure. DES-exposure from postnatal day 1 to 5 inhibited induction of p63 in cervicovaginal epithelium via epithelial ER\u03b1. The inhibitory effect of DES was transient, and most cervicovaginal epithelial cells recovered expression of p63 by 2 days after discontinuation of DES-treatment. However,some cervicovaginal epithelial cells failed to express p63, remained columnar and persisted into adulthood as adenosis.<\/jats:p>","DOI":"10.1242\/dev.01038","type":"journal-article","created":{"date-parts":[[2004,3,9]],"date-time":"2004-03-09T01:23:43Z","timestamp":1078795423000},"page":"1639-1649","source":"Crossref","is-referenced-by-count":97,"title":["Roles of p63 in the diethylstilbestrol-induced cervicovaginal adenosis"],"prefix":"10.1242","volume":"131","author":[{"given":"Takeshi","family":"Kurita","sequence":"first","affiliation":[{"name":"Department of Anatomy, University of California, San Francisco, CA 94143-0452,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alea A.","family":"Mills","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald R.","family":"Cunha","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of California, San Francisco, CA 94143-0452,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042605093546300_REF1","doi-asserted-by":"crossref","unstructured":"Buchanan, D. 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USA94,6535-6540.","DOI":"10.1073\/pnas.94.12.6535"},{"key":"2021042605093546300_REF4","doi-asserted-by":"crossref","unstructured":"Couse, J. F., Dixon, D., Yates, M., Moore, A. B., Ma, L., Maas,R. and\n          Korach, K. S. (2001). Estrogen receptor-alpha knockout mice exhibit resistance to the developmental effects of neonatal diethylstilbestrol exposure on the female reproductive tract. Dev. Biol.238,224-238.","DOI":"10.1006\/dbio.2001.0413"},{"key":"2021042605093546300_REF5","doi-asserted-by":"crossref","unstructured":"Cunha, G. R. (1976). 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. J. Exp. Zool.196,361-370.","DOI":"10.1002\/jez.1401960310"},{"key":"2021042605093546300_REF6","doi-asserted-by":"crossref","unstructured":"Ehrlich, P., Sybert, V. P., Spencer, A. and Stephens, K.(1995). A common keratin 5 gene mutation in epidermolysis bullosa simplex\u2013Weber-Cockayne. J. Invest. Dermatol.104,877-879.","DOI":"10.1111\/1523-1747.ep12607050"},{"key":"2021042605093546300_REF7","unstructured":"Forsberg, J. G. (1976). Animal model of human disease: adenosis and clear-cell carcinomas of vagina and cervix. Am. J. Pathol.84,669-672."},{"key":"2021042605093546300_REF8","unstructured":"Forsberg, J. G. and Kalland, T. (1981). Neonatal estrogen treatment and epithelial abnormalities in the cervicovaginal epithelium of adult mice. Cancer Res.41,721-734."},{"key":"2021042605093546300_REF9","doi-asserted-by":"crossref","unstructured":"Giusti, R. M., Iwamoto, K. and Hatch, E. E.(1995). Diethylstilbestrol revisited: a review of the long-term health effects. Ann. Intern. Med.122,778-788.","DOI":"10.7326\/0003-4819-122-10-199505150-00008"},{"key":"2021042605093546300_REF10","doi-asserted-by":"crossref","unstructured":"Herbst, A. L., Ulfelder, H. and Poskanzer, D. C.(1971). 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