Neonatal estrogen treatment and epithelial abnormalities in the cervicovaginal epithelium of adult mice

Female NMRI mice were given injections of different doses of 17 beta-estradiol, 17 alpha-estradiol, diethylstilbestrol (DES), dienestrol, trans-stilbene, progesterone, testosterone, 5 alpha-dihydrotestosterone, or olive oil for the first 5 days after birth. When the females were killed at 8 weeks after birth, all the estrogens, effective at different dose levels (10(-2) to 5 microgram/day), had resulted in the display by several of the cervicovaginal preparations studied of a heterotopic columnar epithelium (HCE) in regions where females given injections of olive oil, testosterone, 5 alpha-dihydrotestosterone, progesterone, or trans-stilbene had only the normal squamous epithelium. The further fate of the HCE was followed at two later age stages, 36 to 52 weeks and 14 to 17 months. The HCE developed into glandular-like structures penetrating into the stroma and justifying the designation of adenosis. DES resulted in a more pronounced adenosis than did 17 beta-estradiol; in both cases, metaplasia was a striking component of the adenosis regions. Development of adenosis from HCE was dependent upon presence of the ovaries. Some preparations from 44-week-old females given DES injections showed signs of a beginning malignant transformation in the adenosis regions, more evident in 17-month-old females. Among the 23 preparations in the latter group, 8 had changes morphologically indicating malignancy with examples of adenocarcinoma, mixed carcinoma, and squamous carcinoma. Because of the seemingly low aggressive nature of this malignancy, the term "pseudocarcinoma" is discussed. Ten- to 12-week-old BALB/c and C57BL/6 females given DES injections neonatally had HCE in the uterine cervix and vaginal fornices after neonatal DES injections. Differences in extension of HCE were observed after DES injections for three different 5-day periods in th neonatal and immature stages of NMRI females. An interaction between different DES-sensitive parameters to result in the pseudocarcinomas is discussed.