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Fig. 5. Expression of differentiation markers in the DES-induced uterine and cervicovaginal epithelial lesions. Differentiation marker expression was examined in the serial sections of vaginal adenosis (A-D), cervical adenosis (E-G) and uterine SQM (H-J) in the OVX adult (P60) mice neonatally treated with DES. The openings of adenotic glands in the vagina are indicated by black arrows (D). Green and red arrows indicate columnar and squamous cells, respectively. Epithelial cells in cervicovaginal adenosis were negative for p63 (A,E) and K14 (B,F) and expressed PR in the uterine pattern (C,G). Thus, adenotic epithelium was strongly positive for PR in the absence of E₂ (in ovariectomized host, C and G). In the cervix, coexisting squamous cervical epithelium retained the normal cervicovaginal phenotype and was negative for PR in the absence of E₂ (G). In the vaginal epithelium of neonatally DES-exposed mice, PR (C), C/EBP-ß, involucrin and K10 (not shown) were constitutively activated. Accordingly, in the vagina PR was detected not only in the adenotic but in the entire vaginal epithelium (C) in the absence of E₂. In the adenotic epithelium, ER was also strongly expressed (D). Metaplastic squamous cells in the uterus were positive for ER (not shown), p63 and K14 (H and I). In the absence of E₂, PR (J) was undetectable in the SQM (red arrows), while coexisting columnar UtE was strongly positive for PR (green arrows). In p63⁺ uterine grafts, DES induced squamous cells, which were positive for p63 (K) and K14 (L). By contrast, K14 positive squamous epithelial cells were never detected in the p63^–/– uterine grafts (M). Scale bar: 50 µm.

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